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1.
  • Andersson, Maria, 1975, et al. (författare)
  • Differential global gene expression response patterns of human endothelium exposed to shear stress and intraluminal pressure
  • 2005
  • Ingår i: J Vasc Res. - : S. Karger AG. - 1018-1172. ; 42:5, s. 441-52
  • Tidskriftsartikel (refereegranskat)abstract
    • We investigated the global gene expression response of endothelium exposed to shear stress and intraluminal pressure and tested the hypothesis that the two biomechanical forces induce a differential gene expression response pattern. Intact living human conduit vessels (umbilical veins) were exposed to normal or high intraluminal pressure, or to low or high shear stress in combination with a physiological level of the other force in a unique vascular ex vivo perfusion system. Gene expression profiling was performed by the Affymetrix microarray technology on endothelial cells isolated from stimulated vessels. Biomechanical forces were found to regulate a very large number of genes in the vascular endothelium. In this study, 1,825 genes were responsive to mechanical forces, which corresponds to 17% of the expressed genes. Among pressure-responsive genes, 647 genes were upregulated and 519 genes were down regulated, and of shear stress-responsive genes, 133 genes were upregulated and 771 down regulated. The fraction of genes that responded to both pressure and shear stimulation was surprisingly low, only 13% of the regulated genes. Our results indicate that the two different stimuli induce distinct gene expression response patterns, which can also be observed when studying functional groups. Considering the low number of overlapping genes, we suggest that the endothelial cells can distinguish between shear stress and pressure stimulation.
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3.
  • Bengts, Sophy, et al. (författare)
  • Altered IL-32 Signaling in Abdominal Aortic Aneurysm
  • 2020
  • Ingår i: Journal of Vascular Research. - : KARGER. - 1018-1172 .- 1423-0135. ; 57:4, s. 236-244
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction and Objective:Interleukin (IL)-32 is a pro-inflammatory cytokine not previously studied in relation to abdominal aortic aneurysm (AAA). The aim of this study was to elucidate the expression and localization of IL-32 in AAA.Methods:Expression and localization of IL-32 in human aortic tissue was studied with immunohistochemical analysis and Western blot (AAA:n= 5; controls:n= 4). ELISA was used to measure IL-32 in human plasma samples (AAA:n= 140; controls:n= 37) and in media from cultured peripheral blood mononuclear cells (PBMCs) from 3 healthy donors. IL-32 mRNA in PBMCs, endothelial cells, aortic smooth muscle cells (SMCs), and aortic tissue samples of AAA (n= 16) and control aortas (n= 9) was measured with qPCR.Results:IL-32 was predominantly expressed in SMCs and T-cell-rich areas. Highest mRNA expression was observed in the intima/media layer of the AAA. A weaker protein expression was detected in non-aneurysmal aortas. Expression of IL-32 was confirmed in isolated T cells, macrophages, endothelial cells, and SMCs, where expression was also inducible by cytokines such as interferon-gamma. There was no difference in IL-32 expression in plasma between patients and controls.Conclusion:IL-32 signaling is altered locally in AAA and could potentially play an important role in aneurysm development. Further studies using animal models would be helpful to study its potential role in AAA disease.
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4.
  • Bentzer, Peter, et al. (författare)
  • Prostacyclin reduces microvascular fluid conductivity in cat skeletal muscle through opening of ATP-dependent potassium channels
  • 1999
  • Ingår i: Journal of Vascular Research. - 1423-0135. ; 36:6, s. 516-523
  • Tidskriftsartikel (refereegranskat)abstract
    • Prostacyclin is suggested to reduce microvascular permeability, but the cellular mechanisms mediating this response in the microvascular endothelial cells are still unknown. Considering that prostacyclin relaxes vascular smooth muscle cells via opening of ATP-dependent potassium channels, and opening of ATP-dependent potassium channels in the endothelial cells is suggested to influence microvascular permeability, this study was designed to test (1) if ATP-dependent potassium channels are involved in the regulation of microvascular hydraulic permeability, (2) if the permeability-reducing effect of prostacyclin is mediated through opening of ATP-dependent potassium channels, and (3) if cAMP is involved in this process. An autoperfused cat calf hindlimb was used as experimental model, and microvascular hydraulic permeability (conductivity) was estimated by a capillary filtration coefficient (CFC) technique. The potassium channel opener PCO-400 (0.5 microg x min(-1) per 100 g muscle, intra-arterially), prostacyclin (1 ng x min(-1) per kg body weight, intravenously) and the cAMP analogue dibutyryl-cAMP (24 microg x min(-1) per 100 g muscle, intra-arterially), decreased CFC to 77, 72 and 69% compared to control, respectively (p < 0.01). The decrease in CFC obtained by these substances was completely restituted after the start of a simultaneous infusion of the ATP-dependent potassium channel blocker glibenclamide (6 microg x min(-1) per 100 g muscle, intra-arterially; p < 0.01). Infusion of glibenclamide alone increased CFC to 107% of control (p < 0.05). In conclusion, the ATP-dependent potassium channels contribute to the regulation of microvascular hydraulic conductivity, and the prostacyclin permeability-reducing effect may act through this mechanism via increase in intracellular cAMP.
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5.
  • Claesson-Welsh, Lena (författare)
  • New Frontiers in VEGF/VEGFR Biology
  • 2015
  • Ingår i: Journal of Vascular Research. - 1018-1172 .- 1423-0135. ; 52, s. 79-79
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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6.
  • Dahan, Diana, et al. (författare)
  • MicroRNA-Dependent Control of Serotonin-Induced Pulmonary Arterial Contraction
  • 2017
  • Ingår i: Journal of Vascular Research. - : S. Karger AG. - 1018-1172 .- 1423-0135. ; 54:4, s. 246-256
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Serotonin (5-HT) is considered to play a role in pulmonary arterial hypertension by regulating vascular remodeling and smooth muscle contractility. Here, arteries from mice with inducible and smooth muscle-specific deletion of Dicer were used to address mechanisms by which microRNAs control 5-HT-induced contraction. Methods: Mice were used 5 weeks after Dicer deletion, and pulmonary artery contractility was analyzed by wire myography. Results: No change was seen in right ventricular systolic pressure following dicer deletion, but systemic blood pressure was reduced. Enhanced 5-HT-induced contraction in Dicer KO pulmonary arteries was associated with increased 5-HT2A receptor mRNA expression whereas 5-HT1B and 5-HT2B receptor mRNAs were unchanged. Contraction by the 5-HT2A agonist TCB-2 was increased in Dicer KO as was the response to the 5-HT2B agonist BW723C86. Effects of Src and protein kinase C inhibition were similar in control and KO arteries, but the effect of inhibition of Rho kinase was reduced. We identified miR-30c as a potential candidate for 5-HT2A receptor regulation as it repressed 5-HT2A mRNA and protein. Conclusion: Our findings show that 5-HT receptor signaling in the arterial wall is subject to regulation by microRNAs and that this entails altered 5-HT2A receptor expression and signaling.
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8.
  • Dreja, Karl, et al. (författare)
  • Increased store-operated Ca2+ entry into contractile vascular smooth muscle following organ culture
  • 2001
  • Ingår i: Journal of Vascular Research. - : S. Karger AG. - 1423-0135 .- 1018-1172. ; 38:4, s. 324-331
  • Tidskriftsartikel (refereegranskat)abstract
    • Ca2+ inflow via store-operated Ca2+ channels was investigated in rings of rat tail and basilar arteries kept in serum-free organ culture, which is known to preserve the contractility of the vascular smooth muscle. After culture for 3-4 days, Ca2+ release from intracellular stores in response to caffeine (20 mM) was augmented 2- to 4-fold. Following depletion of intracellular Ca2+ stores by caffeine and thapsigargin (10 microM), addition of Ca2+ (2.5 mM) caused an increase in the intracellular Ca2+ concentration which was 2-3 times greater in cultured than in freshly dissected rings, and was not affected by verapamil (10 microM). In contrast, L-type Ca2+ channel currents were decreased by 20% after culture. While freshly dissected rings developed no or very little force in response to the addition of Ca2+ after store depletion, cultured rings developed 42% (tail artery) and 60% (basilar artery) of the force of high-K+-induced contractions. These contractions in cultured vessels were insensitive to verapamil but could be completely relaxed by SKF-96365 (30 microM). Store depletion by caffeine increased the Mn2+ quench rate 3- to 4-fold in freshly dissected as well as cultured tail artery, while there was no increase in freshly dissected basilar artery, but a 3-fold increase in cultured basilar artery. Uptake of Ca2+ into intracellular stores was twice as rapid in cultured as in freshly dissected tail artery. This study shows that organ culture of vascular smooth muscle tissue causes changes in Ca2+ handling, resembling the pattern seen in dedifferentiating smooth muscle cells in culture, although contractile properties are maintained.
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9.
  • Dull, RO, et al. (författare)
  • Syndecan-1 and Glypican-1 Knockout Alters Body Water Balance and Urine Response to Fluid Challenge in Mice
  • 2021
  • Ingår i: Journal of vascular research. - : S. Karger AG. - 1423-0135 .- 1018-1172. ; 58:1, s. 58-64
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Syndecan-1 (Sdc-1) and glypican-1 (Gpc-1) are 2 important proteoglycans found in the glycocalyx and believed to govern transvascular distribution of fluid and protein. In this translational study, we assessed Sdc-1 and Gpc-1 knockout (KO) on whole body water balance after an intravenous volume challenge. Sdc-1 and Gpc-1 KO mice had higher starting blood water content versus strain-matched controls. Sdc-1 KO mice exhibited a significantly higher diuretic response (87%; <i>p</i> &#x3c; 0.05), higher excreted volume/infusion volume ratio (<i>p</i> &#x3c; 0.01), higher extravascular/infused ratio, and greater tissue water concentration (60 vs. 52%). Collectively, these suggest differences in kidney response and greater fluid efflux from peripheral vessels. The CD1 strain and Gpc-1 KO had a 2–3-fold larger urine output relative to C57 strain, but Gpc-1 KO reduced the excreted/infused ratio relative to controls (<i>p</i> &#x3c; 0.01) and they maintained plasma dilution longer. Thus, genetic KO of Sdc-1 and Gpc-1 resulted in markedly different phenotypes. This work establishes the feasibility of performing fluid balance studies in mice.
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10.
  • Emilsson, K, et al. (författare)
  • Vascular effects of proteinase-activated receptor 2 agonist peptide
  • 1997
  • Ingår i: Journal of Vascular Research. - 1423-0135. ; 34:4, s. 267-272
  • Tidskriftsartikel (refereegranskat)abstract
    • Proteinase-activated receptor 2 (PAR-2) is a G protein-coupled receptor related to the thrombin receptor. PAR-2 can be activated by trypsin and by synthetic peptides corresponding to the new amino terminus generated by activating proteolytic cleavage. We show in this report that intravenous injection of PAR-2 agonist peptides has dramatic effects on arterial blood pressure in anesthetized rats. The peptide SLIGRLETQPPI, at 150 nmol/kg, transiently decreased the mean arterial pressure from 104 to 60 mm Hg. The hypotensive response was dose-dependent, and was not secondary to effects on central vasoregulatory systems, heart rate, or the kidneys. A nitric oxide synthase inhibitor attenuated the hypotensive response induced by the PAR-2 agonist peptide. Further experiments in vitro, on preparations of rat femoral artery and vein, showed that PAR-2 agonist peptide elicited a dose-dependent relaxation of both types of vessel. Removal of the endothelium abolished the agonist peptide-induced relaxation. Our results demonstrate that activation of PAR-2 can modulate vascular tone, and that this response was an effect mediated at least partly by nitric oxide. The effect on blood vessels further suggests that the physiological activator of this proteolytically activated receptor is an enzyme present and active in the blood, possibly after a vascular injury.
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11.
  • Eriksson, L, et al. (författare)
  • Glucagon-Like Peptide-1 Receptor Activation Does not Affect Re-Endothelialization but Reduces Intimal Hyperplasia via Direct Effects on Smooth Muscle Cells in a Nondiabetic Model of Arterial Injury
  • 2015
  • Ingår i: Journal of vascular research. - : S. Karger AG. - 1423-0135 .- 1018-1172. ; 52:1, s. 41-52
  • Tidskriftsartikel (refereegranskat)abstract
    • Diabetic patients have an increased risk of restenosis and late stent thrombosis after angioplasty, i.e. complications that are related to a defective re-endothelialization. Exendin-4, a stable glucagon-like peptide (GLP)-1 receptor agonist, has been suggested to influence the formation of intimal hyperplasia and to increase endothelial cell proliferation in vitro. Thus, the aim of this study was to investigate the mechanisms by which treatment with exendin-4 could influence re-endothelialization and intimal hyperplasia after vascular injury. <b><i>Methods:</i></b> Sprague-Dawley rats were subjected to balloon injury of the left common carotid artery and treated for 4 weeks with exendin-4 or vehicle. Intimal hyperplasia and vessel wall elasticity were monitored noninvasively by high-frequency ultrasound, and re-endothelialization was evaluated upon sacrifice using Evans blue dye. <b><i>Results and Conclusion:</i></b> Exendin-4 selectively reduced the proliferation of smooth muscle cells (SMCs) and intimal hyperplasia in vivo without affecting the re-endothelialization process, but treatment with exendin-4 improved arterial wall elasticity. Our data also show that exendin-4 significantly decreased the proliferation and increased the apoptosis of SMCs in vitro, effects that appear to be mediated through cAMP signaling and endothelial nitric oxide synthase following GLP-1 receptor activation. Together, these effects of exendin-4 are highly desirable and may lead to an improved outcome for patients undergoing vascular interventions.
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12.
  • Fagerberg, Björn, 1943, et al. (författare)
  • Differences in lesion severity and cellular composition between in vivo assessed upstream and downstream sides of human symptomatic carotid atherosclerotic plaques
  • 2010
  • Ingår i: Journal of Vascular Surgery. - 1423-0135. ; 47:3, s. 221-230
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The heterogeneous structure of carotid atherosclerotic plaques may be better understood if it is related to blood flow variations, influencing gene expression and cellular functions. Upstream of the maximum stenosis there is laminar blood flow and high shear stress, downstream there is turbulence and low shear stress. We studied if these variations were associated with differences in plaque morphology and composition between sites located up- and downstream of the maximum stenosis in symptomatic carotid plaques. Methods: Patients with symptomatic carotid stenosis were examined with magnetic resonance angiography to localize the maximum stenosis in-vivo, prior to endarterectomy. In 41 endarterectomized specimens, transverse tissue sections prepared up- and downstream of the maximum stenosis were compared using histopathology and immunohistochemistry. Results: The location of maximum stenosis relative the carotid bifurcation varied considerably between plaques. Compared with the downstream side, the upstream side of the stenosis had higher incidence of severe lesions with cap rupture and intraplaque hemorrhage, more macrophages, less smooth muscle cells and more collagen. Conclusions: The up- and downstream sides of symptomatic carotid plaques differed in plaque morphology and composition. This implies that the intraplaque location of sampling sites may be a confounding factor in studies of atherosclerotic plaques.
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13.
  • Fogelstrand, Per, 1971, et al. (författare)
  • Increased Vascular Injury Reduces the Degree of Intimal Hyperplasia following Angioplasty in Rabbits.
  • 2011
  • Ingår i: Journal of vascular research. - : S. Karger AG. - 1423-0135 .- 1018-1172. ; 48:4, s. 307-15
  • Tidskriftsartikel (refereegranskat)abstract
    • Background/Aims: Formation of intimal hyperplasia following angioplastic procedures can lead to complications, including restenosis and accelerated atherosclerosis. The vessel wall media is a main source of neointimal cells. However, evidence suggests that there are additional cell sources, such as the adventitia. Here we investigate whether an extensive loss of vascular smooth muscle cells (VSMCs) in the media results in less intimal hyperplasia or if there is compensatory cell recruitment from the adventitia. Methods:A balloon catheter was pulled through the rabbit carotid artery 4 times (major injury) or 2 times (minor injury). Adventitial cells were labeled with 5-bromo-2-deoxyuridine or PKH26. Results:The major injury, but not the minor injury, resulted in a complete loss of VSMCs in large parts of the media and significant leukocyte infiltration. The major injury resulted in less neointima compared with the minor injury. The thinnest neointima was seen at the most injured parts of the media in the major injury group. Cell-tracking experiments showed that the media, but not the adventitia, served as a source of neointimal cells. Conclusion: An augmented angioplastic injury with extensive VSMC loss in rabbits reduced the degree of intimal hyperplasia. No compensatory recruitment of neointimal cells from the adventitia occurred.
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14.
  • Forte, A, et al. (författare)
  • c-Myc antisense oligonucleotides preserve smooth muscle differentiation and reduce negative remodelling following rat carotid arteriotomy
  • 2005
  • Ingår i: Journal of Vascular Research. - : S. Karger AG. - 1423-0135 .- 1018-1172. ; 42:3, s. 214-225
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: The vascular biology of restenosis is complex and not fully understood, thus explaining the lack of effective therapy for its prevention in clinical settings. The role of c-Myc in arteriotomy-induced stenosis, smooth muscle cell (SMC) differentiation and apoptosis was investigated in rat carotids applying full phosphorothioate antisense ( AS) oligonucleotides (ODNs). Methods: Carotid arteries from WKY rats were submitted to arteriotomy and to local application of ODNs through pluronic gel. Apoptosis ( deoxynucleotidyl transferase-mediated dUTP nick end-labelling), SMC differentiation (SM22 immunofluorescence) and vessel morphology and morphometry ( image analysis) were determined 2, 5 and 30 days after injury, respectively. Results: AS ODNs induced a 60% decrease of target c-Myc mRNA 4 h after surgery in comparison to control sense ( S) and scrambled ODN-treated carotids (p < 0.05). A significant 37 and 50% decrease in SM22 protein in the media of S ODN-treated and untreated carotids was detected when compared to uninjured contralateral arteries (p < 0.05). This reduction in SM22 expression was prevented in AS ODN-treated carotids. Stenosis was mainly due to adventitial constrictive remodelling. Lumen area in AS ODN-treated carotids was 35% greater than in control arteries 30 days after surgery (p < 0.05). TUNEL assay revealed increased apoptosis in AS ODN-treated carotids (p < 0.05). Conclusions: c-Myc AS ODNs reduce arteriotomy-induced negative remodelling. This is accompanied by maintained SMC differentiation and greater apoptosis. The combination of reduced c-Myc-induced proliferation and increased apoptosis may thus underlie the less severe remodelling upon treatment with c-Myc mRNA AS ODN.
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15.
  • Gabrielson, Marike, et al. (författare)
  • Altered PPARγ coactivator-1 alpha expression in abdominal aortic aneurysm : Possible effects on mitochondrial biogenesis
  • 2016
  • Ingår i: Journal of Vascular Research. - : S. Karger. - 1018-1172 .- 1423-0135. ; 53:1-2, s. 17-26
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Abdominal aortic aneurysm (AAA) is a complex and deadly vascular disorder. The pathogenesis of AAA includes destruction and phenotypic alterations of the vascular smooth muscle cells (VSMCs) and aortic tissues. PPARγ coactivator-1 alpha (PGC1α) regulates VSMC migration and matrix formation and is a major inducer of mitochondrial biogenesis and function, including oxidative metabolism. Methods: Protein and gene expression of PGC1α and markers for mitochondria biogenesis and cell type-specificity were analysed in AAA aortas from humans and mice and compared against control aortas. Results: Gene expression of PPARGC1A was decreased in human AAA and angiotensin (Ang) II-induced AAA in mice when compared to control vessels. However, high expression of PGC1α was detected in regions of neovascularisation in the adventitia layer. In contrast, the intima/media layer of AAA vessel exhibited defective mitochondrial biogenesis as indicated by low expression of PPARGC1A, VDAC, ATP synthase and citrate synthase. Conclusion: Our results suggest that mitochondrial biogenesis is impaired in AAA in synthetic SMCs in the media, with the exception of newly formed supporting vessels in the adventitia where the mitochondrial markers seem to be intact. To our knowledge, this is the first study investigating PGC1α and mitochondria biogenesis in AAA.
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16.
  • Gidlöf, Andreas C., et al. (författare)
  • Differences in retinol metabolism and proliferative response between neointimal and medial smooth muscle cells
  • 2006
  • Ingår i: Journal of Vascular Research. - : S. Karger AG. - 1018-1172 .- 1423-0135. ; 43:4, s. 392-398
  • Tidskriftsartikel (refereegranskat)abstract
    • Vascular disease is multifactorial and smooth muscle cells (SMCs) play a key role. Retinoids have been shown to influence many disease-promoting processes including proliferation and differentiation in the vessel wall. Phenotypic heterogeneity of vascular SMCs is a well-known phenomenon and phenotypic modulation of SMCs precedes intimal hyperplasia. The SMCs that constitute the intimal hyperplasia demonstrate a distinct phenotype and differ in gene expression compared to medial SMCs. Cellular retinol-binding protein-1 (CRBP-I), involved in retinoid metabolism, is highly expressed in intimal SMCs, indicating altered retinoid metabolism in this subset of cells. The aim of this study was to evaluate the metabolism of all-trans ROH (atROH), the circulating prohormone to active retinoids, in vascular SMCs of different phenotypes. The results show an increased uptake of atROH in intimal SMCs compared to medial SMCs as well as increased expression of the retinoid-metabolizing enzymes retinol clehydrogenase-5 and retinal dehydrogenase-1 and, in conjunction with this gene expression, increased production of all-trans retinoic acid (atRA). Furthermore, the retinoic acid-catabolizing enzyme CYP26A1 is expressed at higher levels in medial SMCs compared to intimal SMCs. Thus, both retinoid activation and deactivation processes are in operation. To analyze if the difference in ROH metabolism was also correlated to differences in the biological response to retinol, the effects of ROH on proliferation of SMCs with this phenotypic heterogeneity were studied. We found that intimal SMCs showed a dose- and time-dependent growth inhibition when treated with atROH in contrast to medial SMCs, in which atROH had a mitogenic effect. This study shows, for the first time, that (1) vascular SMCs are able to synthesize biologically active atRA from the prohormone atROH, (2) intimal SMCs have a higher capacity to internalize atROH and metabolize atROH into atRA compared to medial SMCs and (3) atROH inhibits growth of intimal SMCs, but induces medial SMC growth.
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17.
  • Gidlöf, Olof, et al. (författare)
  • Extracellular Uridine Triphosphate and Adenosine Triphosphate Attenuate Endothelial Inflammation through miR-22-Mediated ICAM-1 Inhibition.
  • 2015
  • Ingår i: Journal of Vascular Research. - : S. Karger AG. - 1423-0135 .- 1018-1172. ; 52:2, s. 71-80
  • Tidskriftsartikel (refereegranskat)abstract
    • Adenosine and uridine triphosphate (ATP and UTP) can act as extracellular signalling molecules, playing important roles in vascular biology and disease. ATP and UTP acting via the P2Y2-receptor have, for example, been shown to regulate endothelial dilatation, inflammation and angiogenesis. MicroRNAs (miRNAs), a class of regulatory, short, non-coding RNAs, have been shown to be important regulators of these biological processes. In this study, we used RNA deep-sequencing to explore changes in miRNA expression in the human microvascular endothelial cell line HMEC-1 upon UTP treatment. The expression of miR-22, which we have previously shown to target ICAM-1 mRNA in HMEC-1, increased significantly after stimulation. Up-regulation of miR-22 and down-regulation of cell surface ICAM-1 were confirmed with qRT-PCR and flow cytometry, respectively. siRNA-mediated knockdown of the P2Y2-receptor abolished the effect of UTP on miR-22 transcription. Leukocyte adhesion was significantly inhibited in HMEC-1 following miR-22 overexpression and treatment with UTP/ATP. In conclusion, extracellular UTP and ATP can attenuate ICAM-1 expression and leukocyte adhesion in endothelial cells through miR-22. © 2015 S. Karger AG, Basel.
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18.
  • Goncalves, Isabel, et al. (författare)
  • Elastin- and Collagen-Rich Human Carotid Plaques Have Increased Levels of the Cysteine Protease Inhibitor Cystatin C.
  • 2008
  • Ingår i: Journal of Vascular Research. - : S. Karger AG. - 1423-0135 .- 1018-1172. ; 45:5, s. 395-401
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Cystatin C is a major inhibitor of the elastin- and collagen-degrading cysteine proteases and may therefore have an important role in preserving atherosclerotic plaque stability. In this study we analyzed the associations between human carotid plaque cystatin C expression and the plaque content of collagen and elastin. Methods: Thirty-one plaques were removed by endarterectomy and homogenized. Cystatin C levels were analyzed by densitometry of Western blots and elastin and collagen levels were determined colorimetrically. Results: The plaque content of cystatin C correlated with total elastin (r = 0.58, p = 0.001) and collagen (r = 0.50, p = 0.004), as well as with cross-linked forms of elastin (r = 0.42, p = 0.022) and collagen (r = 0.52, p = 0.003). Immunohistochemical analysis demonstrated that cystatin C colocalized with elastin and collagen. No correlation was seen between cystatin C and the amount of degraded elastin or collagen in plaques. Conclusion: The positive correlation between cystatin C levels and collagen and elastin levels in plaques supports the notion that cystatin C plays an important role in maintaining atherosclerotic plaque stability. Copyright (c) 2008 S. Karger AG, Basel.
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19.
  • Haarhaus, Mathias, et al. (författare)
  • Calcifying Human Aortic Smooth Muscle Cells Express Different Bone Alkaline Phosphatase Isoforms, Including the Novel B1x Isoform
  • 2013
  • Ingår i: Journal of Vascular Research. - : S. Karger. - 1018-1172 .- 1423-0135. ; 50:2, s. 167-174
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Vascular calcification, causing cardiovascular morbidity and mortality, is associated with hyperphosphatemia in chronic kidney disease (CKD). In vitro, phosphate induces transdifferentiation of vascular smooth muscle cells to osteoblast-like cells that express alkaline phosphatase (ALP). In vivo, raised serum ALP activities are associated with increased mortality. A new bone ALP isoform (B1x) has been identified in serum from CKD patients. The present study investigated the different ALP isoforms in calcifying human aortic smooth muscle cells (HAoSMCs). Methods: HAoSMCs were cultured for 30 days in medium containing 5 or 10 mmol/l beta-glycerophosphate in the presence or absence of the ALP-specific inhibitor tetramisole. Results: All known bone-specific ALP (BALP) isoforms (B/I, B1x, B1 and B2) were identified in HAoSMCs. beta-Glycerophosphate stimulated calcification of HAoSMCs, which was associated with increased BALP isoforms B/I, B1x and B2. Tetramisole inhibited the beta-glycerophosphate-induced HAoSMC calcification, which was paralleled by the inhibition of the B1x and B/I, but not the other isoforms. Conclusions: HAoSMCs express the four known BALP isoforms. B/I, B1x and B2 could be essential for soft tissue calcification. B/I and B1x were more affected by tetramisole than the other isoforms, which suggests different biological functions during calcification of HAoSMCs.
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20.
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21.
  • Hansen-Schwartz, Jacob, et al. (författare)
  • Endothelium-Dependent Relaxant Responses to Selective 5-HT(1B/1D) Receptor Agonists in the Isolated Middle Cerebral Artery of the Rat.
  • 2003
  • Ingår i: Journal of Vascular Research. - : S. Karger AG. - 1423-0135 .- 1018-1172. ; 40:6, s. 561-566
  • Tidskriftsartikel (refereegranskat)abstract
    • The vasomotor effects of triptans in the middle cerebral artery (MCA) of rats were studied using the pressurised arteriography method and in vitro vessel baths. Using the arteriograph, MCAs from Sprague-Dawley rats were mounted on two glass micropipettes, pressurised to 85 mm Hg and luminally perfused. Luminally added 5- hydroxytryptamine (5-HT), sumatriptan and rizatriptan induced maximal dilatations of 22 ± 4, 10 ± 2 and 13 ± 5%, respectively, compared to the resting diameter. The relaxant effect of sumatriptan was blocked by the 5- HT<sub>1B/1D</sub> receptor selective antagonist GR 55562 (10<sup>–6</sup><i>M</i>). The use of N<sup>ω</sup>-nitro-<i>L</i>-arginine and charybdotoxin revealed that the dilatation involved both nitric oxide and endothelially derived hyperpolarising factor. Thus, the earlier demonstrated expression of 5-HT<sub>1B/1D</sub> immunoreactivity in the endothelium may well translate into a relaxant response to 5-HT and triptans. Using the vessel bath technique, MCA segments were mounted on two metal wires. The relaxant responses to sumatriptan could not be reproduced using this model; instead, weak contractile responses (6 ± 3% of submaximal contractile capacity) were observed. The difference in observations between the experimental models may be related to the maintenance of shear stress in the arteriograph.
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22.
  • Holm, Anders, et al. (författare)
  • The G Protein-Coupled Estrogen Receptor 1 (GPER1/GPR30) Agonist G-1 Regulates Vascular Smooth Muscle Cell Ca Handling.
  • 2013
  • Ingår i: Journal of Vascular Research. - : S. Karger AG. - 1423-0135 .- 1018-1172. ; 50:5, s. 421-429
  • Tidskriftsartikel (refereegranskat)abstract
    • The G protein-coupled estrogen receptor GPER1/GPR30 is implicated in blood pressure regulation but the mechanisms are not identified. Here, we hypothesize that GPER1 controls blood pressure by regulating vascular smooth muscle cell Ca(2+) handling. Treatment with the GPER1 agonist G-1 (in the µM concentration range) acutely reduced spontaneous and synchronous Ca(2+) spike activity in A7r5 vascular smooth muscle cells expressing mRNA for GPER1. Furthermore, G-1 (1 µM) attenuated the thromboxane A2 analogue U46619-stimulated Ca(2+) spike activity but had no effect on the U46619-induced increase in the basal level of Ca(2+). The voltage-sensitive L-type Ca(2+) channel blocker nifedipine (100 nM) reduced Ca(2+) spike activity similar to G-1. Pharmacological, but not physiological, concentrations of the estrogen 17β-estradiol reduced Ca(2+) spike activity. The GPER1 antagonist G-15 blocked G-1-induced downregulation of Ca(2+) spike activity, supporting a GPER1-dependent mechanism. G-1 (1 µM) and nifedipine (100 nM) attenuated the 30-mM KCl-evoked rise in intracellular Ca(2+) concentration, suggesting that G-1 blocks inflow of Ca(2+) via voltage-sensitive Ca(2+) channels. In conclusion, we demonstrate that the GPER1 agonist G-1 regulates vascular smooth muscle cell Ca(2+) handling by lowering Ca(2+) spike activity, suggesting a role for this mechanism in GPER1-mediated control of blood pressure. © 2013 S. Karger AG, Basel.
  •  
23.
  • Holm, Anders, et al. (författare)
  • The GPER1 Agonist G-1 Attenuates Endothelial Cell Proliferation by Inhibiting DNA Synthesis and Accumulating Cells in the S and G2 Phases of the Cell Cycle.
  • 2011
  • Ingår i: Journal of Vascular Research. - : S. Karger AG. - 1423-0135 .- 1018-1172. ; 48:4, s. 327-335
  • Tidskriftsartikel (refereegranskat)abstract
    • G protein-coupled receptor 30 (GPR30) or G protein-coupled estrogen receptor 1 (GPER1) is expressed in the vasculature, but the importance of vascular GPER1 remains to be clarified. Here we investigate effects of the GPER1 agonist G-1 on endothelial cell proliferation using mouse microvascular endothelial bEnd.3 cells. The bEnd.3 cells express mRNA for GPER1. The bEnd.3 cells expressed both ERα and ERβ immunoreactivities. Treatment with G-1 reduced DNA synthesis and cell number with IC(50) values of about 2 μM. GPER1 siRNA prevented G-1-induced attenuation of DNA synthesis. G-1 accumulated cells in S and G2 phases of the cell cycle, suggesting that G-1 blocks transition between G2 and M. G-1 had no effect on DNA synthesis in COS-7 cells only weakly expressing GPER1 mRNA. 17β-Estradiol had no effect on DNA synthesis in physiological concentrations (nM). The ER blocker ICI182780 reduced DNA synthesis with similar potency as G-1. Treatment with the ERK/MAP kinase inhibitor PD98059 had no effect on G-1-induced attenuation of DNA synthesis. G-1- induced antiproliferation was observed not only in bEnd.3 cells but also in human umbilical vein endothelial cells and HMEC-1 endothelial cells. We conclude that the GPER1 agonist G-1 attenuates endothelial cell proliferation via inhibition of DNA synthesis and by accumulation of cells in S and G2.
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24.
  • Jatta, Ken, et al. (författare)
  • Lipopolysaccharide-induced cytokine and chemokine expression in human carotid lesions
  • 2005
  • Ingår i: Journal of Vascular Research. - : S. Karger AG. - 1018-1172 .- 1423-0135. ; 42:3, s. 266-271
  • Tidskriftsartikel (refereegranskat)abstract
    • The release of cytokines and chemokines from activated immune-competent cells plays a crucial role in determining the pathology of the atherogenic progress. We investigated the effect of bacterial lipopolysaccharide (LPS) on cytokine/chemokine expression in carotid lesions and normal renal arteries. The lesions or renal arteries were incubated for 6 h at 37 degrees C in serum-free media treated with or without LPS. After LPS treatment, increased protein levels of IL-1beta, IL-6, IL-8, IL-10, TNF-alpha and MCP-1 were observed in the culture medium from the lesions measured with cytometric bead array. We were able to detect the induction of IL-1beta, IL-6, IL-8, IL-10, TNF-alpha and MCP-1 mRNA in the lesions after stimulation with LPS using real-time PCR. In renal arteries, LPS also induces mRNA expression of all chemokines and cytokines investigated with the exception of IL-6. However, LPS induces significantly higher levels of TNF-alpha, IL-1beta and IL-10 mRNA in lesions compared to renal arteries. The results suggest that infectious agents are capable of enhancing the production of cytokines/chemokines in an already ongoing inflammatory process such as in atherosclerosis, and that low levels of circulating LPS may affect the levels of pro-inflammatory cytokines much more in atherosclerotic vessels than in normal vessels and may contribute to the development of the atherosclerotic lesion.
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25.
  • Laine, M, et al. (författare)
  • Few Internal Iliac artery Aneurysms Rupture under 4 cm
  • 2017
  • Ingår i: Journal of Vascular Research. - : Elsevier BV. - 1018-1172 .- 1423-0135 .- 0741-5214. ; 65:1, s. 76-81
  • Tidskriftsartikel (refereegranskat)abstract
    • ObjectiveThis study investigated the diameter of internal iliac artery (IIA) aneurysms (IIAAs) at the time of rupture to evaluate whether the current threshold diameter for elective repair of 3 cm is reasonable. The prevalence of concomitant aneurysms and results of surgical treatment were also investigated.MethodsThis was a retrospective analysis of patients with ruptured IIAA from seven countries. The patients were collected from vascular registries and patient records of 28 vascular centers. Computed tomography images taken at the time of rupture were analyzed, and maximal diameters of the ruptured IIA and other aortoiliac arteries were measured. Data on the type of surgical treatment, mortality at 30 days, and follow-up were collected.ResultsSixty-three patients (55 men and 8 women) were identified, operated on from 2002 to 2015. The patients were a mean age of 76.6 years (standard deviation, 9.0; range 48-93 years). A concomitant common iliac artery aneurysm was present in 65.0%, 41.7% had a concomitant abdominal aortic aneurysm, and 36.7% had both. IIAA was isolated in 30.0%. The mean maximal diameter of the ruptured artery was 68.4 mm (standard deviation, 20.5 mm; median, 67.0 mm; range, 25-116 mm). One rupture occurred at <3 cm and four at <4 cm (6.3% of all ruptures). All patients were treated, 73.0% by open repair and 27.0% by endovascular repair. The 30-day mortality was 12.7%. Median follow-up was 18.3 months (interquartile range, 2.0-48.3 months). The 1-year Kaplan-Meier estimate for survival was 74.5% (standard error, 5.7%).ConclusionsIIAA is an uncommon condition and mostly coexists with other aortoiliac aneurysms. Follow-up until a diameter of 4 cm seems justified, at least in elderly men, although lack of surveillance data precludes firm conclusions. The mortality was low compared with previously published figures and lower than mortality in patients with ruptured abdominal aortic aneurysm.Abdominal aortic aneurysm (AAA) is the most common and studied aneurysm. Aneurysms of the iliac arteries are found considerably less often, and epidemiologic data on these do not exist. In many cases iliac artery aneurysms coexist with aortic aneurysms: ∼10% to 20% of patients with AAA also have a concomitant aneurysm in the iliac arteries.1 The artery most often affected is the common iliac artery (CIA), followed by the internal iliac artery (IIA), also called the hypogastric artery. In the case of isolated aneurysms in the iliac arteries, without involvement of the aorta, the most common location is the IIA.2 Aneurysms of the external iliac artery are extremely rare, possibly because these arteries originate later in development from a different cell population than the distal aorta and the CIA and IIA. Studies on IIA aneurysms (IIAAs) are scarce owing to the rarity of the condition. The existing literature consists primarily of case reports and small patient series. No prospective studies on IAAs exist.According to the literature, IAAs have a high rupture and mortality rate even in elective cases, possibly because of their deep location in the pelvis.3 The etiology and risk factors of IAA seem to be the same as AAA.4 Iliac aneurysms are mostly degenerative but can also be mycotic or caused by genetic disorders such as Marfan or Ehlers-Danlos syndromes. Traumatic aneurysms in the iliac arteries have also been described; for example, caused by iatrogenic trauma from hip, lumbar, or gynecologic operations. A mainly historical subpopulation of young women with IIAA caused by trauma from pregnancy and delivery has been described.5 and 6IAAs cause symptoms more often than AAA because of compression of pelvic structures such as ureters, bladder, veins, or lumbar nerves. Wilhelm et al7 reported that 53% of published isolated IIAA cases were symptomatic, not including the ruptured ones (31%). The high proportion of symptomatic patients in these older reports may partly be explained, however, by the fact that most of these cases were from time before widespread use of modern imaging. IIAA are not easily discovered with clinical examination because of their location8 but are detected increasingly often as a result of imaging and screening programs.Because the studies on IIAAs are scarce, the natural history is virtually unknown. A widely used threshold for elective repair is 3 cm, originally suggested by McCready et al9 because their series did not include any ruptures under that diameter. However, only seven ruptures were included in that report. The reference list of this article illustrates that most of the papers on this subject were published when open repair was the only treatment option. Nowadays endovascular treatment is the first option in many centers.10The aim of this study was to investigate at what diameter IIAAs tend to rupture and whether the current operative threshold of 3 cm is rational. Secondary aims were to assess the prevalence of concomitant aortoiliac aneurysms, treatment patterns, and the results of treatment.
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26.
  • Laskowski, Marta, 1991, et al. (författare)
  • Potassium-Channel-Independent Relaxing Influence of Adipose Tissue on Mouse Carotid Artery
  • 2017
  • Ingår i: Journal of Vascular Research. - : S. Karger AG. - 1018-1172 .- 1423-0135. ; 54:1, s. 51-57
  • Tidskriftsartikel (refereegranskat)abstract
    • Since the cardiovascular consequences of obesity reportedly vary in different types of obesity, we investigated the influence of adipose tissue from different locales on the phenylephrine- induced tone of the mouse carotid artery. Vessels were mounted in a Mulvany-Halpern-type wire myograph, and adipose tissue, from the back (brown) or mesenteric or inguinal subcutaneous (white), was placed around the artery. Contractile responses to phenylephrine were not affected by brown adipose tissue but were reduced (p < 0.001) by either type of white adipose tissue, with no difference between the 2 locales. The relaxing effect persisted in the presence of the Kv7 channel inhibitor XE991 (10,10-bis(4pyridinylmethyl)- 9(10H)-anthracenone), the K-ATP channel inhibitor glibenclamide (1 mu M), or the K-V channel inhibitor 4-amino pyridine (1 mM), as well as after elevation of the extracellular potassium concentration to 30 mM. Contractions of rat carotid artery were equally reduced by mouse and rat subcutaneous adipose tissue. Thus, white, but not brown, adipose tissue reduces the adrenergic contractions of the carotid artery with no differences between the locales of origin, and the effect appears largely independent of potassium channels.
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27.
  • Liang, Min, et al. (författare)
  • Polyamine Synthesis Inhibition Attenuates Vascular Smooth Muscle Cell Migration.
  • 2004
  • Ingår i: Journal of Vascular Research. - : S. Karger AG. - 1423-0135 .- 1018-1172. ; 41:2, s. 141-147
  • Tidskriftsartikel (refereegranskat)abstract
    • Vascular smooth muscle cell migration, occurring after intimal injury, is a substantial clinical problem in atherosclerosis and restenosis after stenting. Here we investigate the effects of polyamine synthesis inhibition on vascular smooth muscle cell migration after maximal and submaximal growth stimulation with PDGF-AB or FCS. Vascular smooth muscle cells were obtained from mouse aorta explants. These cells coexpressed smooth muscle alpha-actin, PDGFRalpha and PDGFRbeta as demonstrated by immunocytochemistry. Treatment with a high (100 ng/ ml) concentration of PDGF-AB stimulated DNA synthesis 6-fold and markedly elevated cell migration. PDGF-AB (100 ng/ml) increased cellular spermidine concentration 2-fold, but had no effect on spermine or putrescine levels. Treatment with the polyamine synthesis inhibitors CGP48664 (1 µM) and DFMO (5 mM) prevented the PDGF-AB-induced increase in spermidine and reduced spermine concentrations, but had no effect on PDGF-AB-stimulated DNA synthesis or cell migration. Cell migration after submaximal stimulation with either PDGF-AB (8 ng/ml) or FCS (8%) was, however, inhibited by the polyamine synthesis blockers. In summary, these data show that polyamine synthesis inhibition attenuates vascular smooth muscle cell migration under submaximal growth-stimulating conditions, suggesting that polyamines participate in regulation of cell migration and that treatment with polyamine synthesis inhibitors might reduce vascular smooth muscle cell migration after intimal injury.
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28.
  • Lindqvist, Anders, et al. (författare)
  • Inhibition of calcium entry preserves contractility of arterial smooth muscle in culture
  • 1997
  • Ingår i: Journal of Vascular Research. - 1423-0135. ; 34:2, s. 103-108
  • Tidskriftsartikel (refereegranskat)abstract
    • The addition of the growth stimulator fetal calf serum (FCS, 10%) to rings of rat tail artery causes an increase in [Ca2+]i, accompanied by contraction. This response was inhibited by the calcium entry blocker verapamil (1 microM). To investigate the effect of Ca2+ entry blockade on growth and contractility, rings of rat tail artery were cultured for 4 days in medium with or without FCS and then mounted for tension registration and stimulated with noradrenaline (NA) or high-K+ solution. In cultured rings growth was quantitated by [3H]-thymidine incorporation and increase in protein contents. FCS in the medium stimulated DNA synthesis by about 2-fold and increased protein contents by about 70%. The growth-stimulated cultured rings developed less force than freshly prepared rings (2.2 +/- 0.3 vs. 8.3 +/- 1.0 mN/mm). The addition of 1 microM verapamil to the medium during culture increased maximal NA-evoked force to 5.0 +/- 0.4 mN/mm but had no effect on the increases in DNA synthesis and protein contents. Force developed by growth-arrested rings, cultured in the absence of FCS, was not different from that of freshly prepared rings (7.2 +/- 0.6 mM/mm). Verapamil did not affect maximal force in these rings. Similar responses were seen when contraction was elicited by high-K+ solution. We conclude that verapamil, present during culture, preserves contractility of arterial smooth muscle, and that this effect is not parallel to inhibition of growth.
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29.
  • Liuba, Petru, et al. (författare)
  • Co-Infection with CHLAMYDIA PNEUMONIAE and HELICOBACTER PYLORI Results in Vascular Endothelial Dysfunction and Enhanced VCAM-1 Expression in ApoE-Knockout Mice.
  • 2003
  • Ingår i: Journal of Vascular Research. - : S. Karger AG. - 1423-0135 .- 1018-1172. ; 40:2, s. 115-122
  • Tidskriftsartikel (refereegranskat)abstract
    • <i>Background:</i> Upregulation of proinflammatory endothelial cell adhesion molecules and decreased bioactivity of endothelial nitric oxide (NO) are important in the pathogenesis of atherosclerosis. We investigated the effects of co-infection with <i>Chlamydia pneumoniae</i> and <i>Helicobacter pylori </i>on these two events in apoE-KO mice. <i>Methods:</i> Thirty-two apoE-KO mice, 8 weeks old, were equally divided into 4 groups. The first 2 groups were infected with either <i>C. pneumoniae</i> or <i>H. pylori,</i> while the 3rd group was infected with both <i>C. pneumoniae</i> and <i>H. pylori</i>. Mice from the 4th group and 4 wild-type mice served as controls. Thoracic and abdominal aortas were harvested after 10 weeks, and staining for vascular cell adhesion molecule-1 (VCAM-1) and intracellular adhesion molecule-1 was analyzed by immunocytochemistry. The endothelial vasomotor responses of thoracic aortas to methacholine were studied in organ chambers in the absence and presence of <i>L</i>-NAME. The plasma levels of nitrate/nitrite were measured. <i>Results:</i> Staining for VCAM-1 was more intense at the branching sites of aortas from mice with co-infection than in mono-infected or noninfected apoE-KO mice. The relaxation responses to methacholine and the plasma levels of nitrate/nitrite were significantly less in the co-infected group than in the other groups (p < 0.05). <i>Conclusion:</i> Co-infection of apoE-KO mice with <i>C. pneumoniae</i> and <i>H. pylori</i> seems to be associated with impaired bioactivity of endothelial NO and increased expression of VCAM-1 at branching sites. The findings may suggest an additive interaction of these pathogens in atherogenesis.
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30.
  • Lovdahl, C, et al. (författare)
  • The synthetic metalloproteinase inhibitor batimastat suppresses injury-induced phosphorylation of MAP kinase ERK1/ERK2 and phenotypic modification of arterial smooth muscle cells in vitro
  • 2000
  • Ingår i: Journal of vascular research. - : S. Karger AG. - 1018-1172 .- 1423-0135. ; 37:5, s. 345-354
  • Tidskriftsartikel (refereegranskat)abstract
    • Smooth muscle cell (SMC) migration and proliferation are important events in the formation of intimal lesions associated with atherosclerosis and restenosis following balloon angioplasty. The extracellular matrix has important functions in modulating SMC structure and function, but less is known about the role of the matrix metalloproteinases (MMPs) and their endogenous tissue inhibitors. The present study investigates the effects of the synthetic MMP inhibitor batimastat (BB94) on vascular SMCs. As experimental model, rat aortic smooth muscle cells in primary and secondary cultures were employed. Electron microscopy was used to investigate the effects of BB94 on the overall phenotypic properties of the cells. Induction of DNA synthesis and migration was studied by thymidine autoradiography and counting of cells moving into an injured zone. Gelatin zymography was used for the detection of BB94-mediated inhibition of injury-induced MMP activity. Phosphorylation of the mitogen-activated protein kinases ERK1/ERK2, two potential mediators of the injury-induced activation of the cells, was measured by Western blotting. The results show that BB94 restrained the phenotypic modulation of vascular SMCs in primary cultures and suppressed injury-induced DNA synthesis and migration. Moreover, the upregulation of ERK1/ERK2 phosphorylation in injured secondary cultures and in cells treated with bFGF was markedly reduced by BB94, whereas TIMP-2 lacked a clear effect. Our data suggest that BB94 inhibits injury-induced activation of vascular SMCs by acting on MMPs as well as other targets.
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31.
  • Lydrup, M L, et al. (författare)
  • Effect of glibenclamide on membrane response to metabolic inhibition in smooth muscle of rat portal vein
  • 1994
  • Ingår i: Journal of Vascular Research. - 1423-0135. ; 31:2, s. 82-91
  • Tidskriftsartikel (refereegranskat)abstract
    • Vascular smooth muscle tone is dependent on oxidative metabolism, a phenomenon of potential importance for the metabolic regulation of blood flow to tissues. The response of the rat portal vein to inhibition of cell respiration by cyanide (0.1-1 mM) is a reduction of its spontaneous myogenic activity. The trains of action potentials triggering phasic contractions are reduced in duration, while the frequency of trains is often somewhat increased as the resting membrane potential in the intervals between spike trains is less negative by 6.5 mV. Glibenclamide (10(-7) M) did not affect the resting membrane potential or spontaneous mechanical activity of oxygenated portal veins, but partly restored the depressed myogenic activity in the presence of cyanide (0.5 mM). The spike trains were longer, while the membrane was depolarized by 3 mV compared with the effects of cyanide alone. Inhibition of both oxidative and glycolytic metabolism by 2 mM NaCN in a medium where glucose was replaced by beta-hydroxybutyrate caused a hyperpolarization which was abolished by 10(-7) M glibenclamide. The relaxing effect of the K+ channel opener cromakalim (5 x 10(-9) to 6.25 x 10(-7) M) was partly antagonized by glibenclamide. Basal cytosolic [Ca2+] was increased by cyanide, while the Ca2+ transients associated with phasic contractions were reduced in duration. This latter effect was partially reversed by glibenclamide. The effect of cyanide on high-K+ contractures, which are associated with sustained membrane depolarization and not dependent on repetitive spike activity, was not influenced by 10(-7) M glibenclamide. The effects of inhibited cell respiration on spontaneous electrical activity seem to reflect a depolarizing drive caused by inhibited active ion exchange mechanisms, modified by a repolarizing drive, possibly from ATP-regulated K+ channels, causing reduced duration of the spike trains. While glibenclamide affects spontaneous activity at all levels of oxidative blockade, glibenclamide-sensitive hyperpolarization is seen only when both oxidative and glycolytic metabolism is inhibited.
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32.
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33.
  • Mellor, Russell H, et al. (författare)
  • Mutations in FOXC2 in humans (lymphoedema distichiasis syndrome) cause lymphatic dysfunction on dependency.
  • 2011
  • Ingår i: Journal of Vascular Research. - : S. Karger AG. - 1018-1172 .- 1423-0135. ; 48:5
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Human lymphoedema distichiasis syndrome (LDS) results from germline mutations in transcription factor FOXC2. In a mouse model, lack of lymphatic and venous valves is observed plus abnormal smooth muscle cell recruitment to initial lymphatics. We investigated the mechanism of lymphoedema in humans with FOXC2 mutations, specifically the effect of gravitational forces on dermal lymphatic function.METHODS: We performed (1) quantitative fluorescence microlymphangiography (FML) on the skin of the forearm (non-swollen region) at heart level, and the foot (swollen region) below heart level (dependent) and then at heart level, and (2) immunohistochemical staining of microlymphatics in forearm and foot skin biopsies, using antibodies to podoplanin, LYVE-1 and smooth muscle actin.RESULTS: FML revealed a marked reduction in fluid uptake by initial lymphatics in the LDS foot during dependency, yet normal uptake (similar to controls) in the same foot at heart level and in LDS forearms. In control subjects, dependency did not impair initial lymphatic filling. Immunohistochemical microlymphatic density in forearm and foot did not differ between LDS and controls.CONCLUSIONS: FOXC2 mutations cause a functional failure of dermal initial lymphatics during gravitational stress (dependency), but not hypoplasia. The results reveal a pathophysiological mechanism contributing to swelling in LDS.
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34.
  • Murugesan, Vignesh, et al. (författare)
  • β-Sarcoglycan Deficiency Reduces Atherosclerotic Plaque Development in ApoE-Null Mice
  • 2017
  • Ingår i: Journal of Vascular Research. - : S. Karger AG. - 1423-0135 .- 1018-1172. ; 54, s. 235-245
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Smooth muscle cells are important for atheroscleroticplaque stability. Their proper ability to communicatewith the extracellular matrix is crucial for maintainingthe correct tissue integrity. In this study, we have investigatedthe role of β-sarcoglycan within the matrix-binding dystrophin-glycoproteincomplex in the development of atherosclerosis.Results: Atherosclerotic plaque developmentwas significantly reduced in ApoE-deficient mice lackingβ-sarcoglycan, and their plaques contained an increase indifferentiated smooth muscle cells. ApoE-deficient micelacking β-sarcoglycan showed a reduction in ovarian adiposetissue and adipocyte size, while the total weight of theanimals was not significantly different. Western blot analysisof adipose tissues showed a decreased activation of proteinkinase B, while that of AMP-activated kinase was increasedin mice lacking β-sarcoglycan. Analysis of plasma in β-sarcoglycan-deficientmice revealed reduced levels of leptin,adiponectin, insulin, cholesterol, and triglycerides but in-creased levels of IL-6, IL-17, and TNF-α. Conclusions: Our resultsindicate that the dystrophin-glycoprotein complex andβ-sarcoglycan can affect the atherosclerotic process. Furthermore,the results show the effects of β-sarcoglycan deficiencyon adipose tissue and lipid metabolism, which mayalso have contributed to the atherosclerotic plaque reduction.
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35.
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36.
  • Norrby, Klas, 1937 (författare)
  • Human apo-lactoferrin enhances angiogenesis mediated by vascular endothelial growth factor in vivo
  • 2004
  • Ingår i: J Vasc Res. - : S. Karger AG. - 1018-1172. ; 41:4, s. 293-304
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Lactoferrin, LF, a multifunctional iron- and heparin-binding protein, present in exocrine body secretions and leukocytes, is remarkably resistant to proteolysis. Ingested bovine iron-unsaturated LF, apo-bLF, suppresses VEGF-A-mediated angiogenesis in a previously described rat mesentery angiogenesis assay, possibly explaining, at least in part, its established anticancer effect in rats and mice. METHODS: Using the same experimental system, we have now studied the effect of (i) ingested human apo-LF, apo-hLF, on angiogenesis mediated by VEGF-A and bFGF, (ii) ingested human iron-saturated LF, holo-hLF, on VEGF-A-mediated angiogenesis and (iii) subcutaneous continuously infused apo-hLF on VEGF-A-mediated angiogenesis. RESULTS: Ingested holo-hLF did not affect VEGF-A-mediated angiogenesis. Ingested apo-hLF (from one and the same batch) significantly enhanced VEGF-A-mediated angiogenesis but did not affect bFGF-mediated angiogenesis. Moreover, subcutaneously infused apo-hLF also significantly stimulated VEGF-A-mediated angiogenesis. CONCLUSION: Taken together, the data suggest that apo-hLF exerts a specific proangiogenic effect in VEGF-A-mediated angiogenesis. Clearly, human and bovine apo-LF exert opposite effects on VEGF-A-induced angiogenesis. Differences in molecular features between human and bovine LFs of possible significance for the outcome are discussed. In hypoxia, compensatory collateral circulation is mediated primarily by VEGF-A. We hypothesize that systemically administered apo-hLF may promote collateral blood vessel formation at hypoxic sites in normal tissue, thus counteracting ischemia and infarction.
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37.
  • Ocaya, Pauline Ajok, 1977-, et al. (författare)
  • CYP26B1 plays a major role in the regulation of all-trans-retinoic acid metabolism and signaling in human aortic smooth muscle cells
  • 2011
  • Ingår i: Journal of Vascular Research. - : S. Karger. - 1018-1172 .- 1423-0135. ; 48:1, s. 23-30
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim: The cytochrome P450 enzymes of the CYP26 family are involved in the catabolism of the biologically active retinoid all-trans-retinoic acid (atRA). Since it is possible that an increased local CYP26 activity would reduce the effects of retinoids in vascular injury, we investigated the role of CYP26 in the regulation of atRA levels in human aortic smooth muscle cells (AOSMCs).Methods: The expression of CYP26 was investigated in cultured AOSMCs using real-time PCR. The metabolism of atRA was analyzed by high-performance liquid chromatography, and the inhibitor R115866 or small interfering RNA (siRNA) was used to suppress CYP26 activity/expression.Results: AOSMCs expressed CYP26B1 constitutively and atRA exposure augmented CYP26B1 mRNA levels. Silencing of the CYP26B1 gene expression or reduction of CYP26B1 enzymatic activity by using siRNA or the inhibitor R115866, respectively, increased atRA-mediated signaling and resulted in decreased cell proliferation. The CYP26 inhibitor also induced expression of atRA-responsive genes. Therefore, atRA-induced CYP26 expression accelerated atRA inactivation in AOSMCs, giving rise to an atRA-CYP26 feedback loop. Inhibition of this loop with a CYP26 inhibitor increased retinoid signaling.Conclusion: The results suggest that CYP26 inhibitors may be a therapeutic alternative to exogenous retinoid administration. Copyright (C) 2010 S. Karger AG, Basel
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38.
  • Persson, BP, et al. (författare)
  • Endotoxin induces differentiated contractile responses in porcine pulmonary arteries and veins
  • 2011
  • Ingår i: Journal of vascular research. - : S. Karger AG. - 1423-0135 .- 1018-1172. ; 48:3, s. 206-218
  • Tidskriftsartikel (refereegranskat)abstract
    • <i>Background/Aims:</i> Sepsis-induced lung injury is characterized by pulmonary hypertension, edema and deteriorated gas exchange. As in vivo studies have indicated that bacterial endotoxin predominantly induces a pulmonary venous constriction, we aimed to investigate effects of endotoxin on isolated porcine pulmonary vessels. <i>Methods:</i> Pulmonary arteries and veins were examined using in vitro isometric force recordings. Endothelin-receptor protein expression and distribution were analyzed by Western blot and immunohistochemistry. Freshly isolated preparations and vessels incubated (24 h) with/without endotoxin (10 µg·ml<sup>–1</sup>) were compared. The contractile responses to phenylephrine, UK14.304, U46619, PGF<sub>2</sub><sub>α</sub>, endothelin-1 (ET-1) and sarafotoxin were recorded, as well as the relaxation in response to acetylcholine, isoproterenol and nitroprusside. <i>Results:</i> In freshly isolated vessels, phenylephrine-induced contractions had a 5-times larger amplitude in arteries than in veins. The amplitude of the contractions in response to sarafotoxin was nearly 2 times larger in veins than in arteries, but there was no difference in responses to ET-1. Endotoxin markedly reduced phenylephrine-induced contractions in both arteries and veins, whereas the responses to ET-1 and sarafotoxin were augmented in veins only. No apparent changes in ET receptor expression or distribution were detected with Western blot or immunohistochemistry. <i>Conclusion:</i> Endotoxin differentially and selectively alters the contractile responses of porcine pulmonary vessels in vitro, towards a situation where the α-1 adrenergic responses of arteries are attenuated and the ET responses of veins are augmented. In situations with high adrenergic activity and high circulating ET levels, such as sepsis, these results may provide a mechanism contributing to pulmonary hypertension and edema formation.
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39.
  • Persson, Johan, et al. (författare)
  • Endogenous Nitric Oxide Reduces Microvascular Permeability and Tissue Oedema during Exercise in Cat Skeletal Muscle.
  • 2003
  • Ingår i: Journal of Vascular Research. - : S. Karger AG. - 1423-0135 .- 1018-1172. ; 40:6, s. 538-546
  • Tidskriftsartikel (refereegranskat)abstract
    • Based on a proposed increase in the release of the vasodilators nitric oxide (NO) and prostacyclin during exercise, and the fact that these substances have vascular permeability-reducing properties, this study was designed to evaluate (1) possible effects of exercise on hydraulic permeability, (2) whether permeability and muscle swelling are reduced by an increased release of NO and prostacyclin during exercise and (3) whether NO and prostacyclin are involved in exercise hyperaemia. The study was performed on an autoperfused cat calf muscle preparation with ligated lymph vessels, and exercise was induced by somatomotor nerve stimulation. Change in microvascular hydraulic permeability was estimated by a capillary filtration coefficient (CFC) technique. We found that the marked muscle volume increase after the start of the exercise gradually decreased, reaching an isovolumetric state within 25 min where CFC had decreased by about 25% (p < 0.05). CFC recovered completely after exercise was stopped. The decrease in CFC was abolished during blockade of endogenous NO by the NO synthase inhibitor <i>L</i>-NAME, but was preserved during blockade of endogenous prostacyclin by tranylcypromine. The muscle volume increase during exercise was about 60% greater with <i>L</i>-NAME than during vehicle or tranylcypromine (p < 0.01). Neither <i>L</i>-NAME nor tranylcypromine had any effect on exercise hyperaemia. We conclude that microvascular hydraulic permeability is reduced during exercise, that this effect reduces exercise-induced muscle swelling, and that the effects are mediated via release of NO. NO and prostacyclin are not involved in exercise hyperaemia.
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40.
  • Rankin, Gregory, et al. (författare)
  • MMP9 Associates with Endothelial Glycocalyx Degradation During Haemorrhagic Fever with Renal Syndrome
  • 2019
  • Ingår i: Journal of Vascular Research. - : S. Karger. - 1018-1172 .- 1423-0135. ; 56, s. 35-35
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Introduction: Haemorrhagic fever with renal syndrome (HFRS) is characterized by fever, hypotension, vascular leakage, thrombocytopenia and renal failure. HFRS in Sweden is caused by the Puumala hantavirus and is spread by viral-infested droppings from bank voles. The health care system has little to offer these patients since there is no antiviral treatment and as of yet there is no vaccine prophylaxis available. We previously showed that a marker of endothelial glycocalyx degradation (Syndecan-1) was associated with disease severity and disseminated intravascular coagulation during HFRS (Connolly-Andersen et al., 2014, Open Forum Infect Dis.).Methods: We analysed the levels of other endothelial glycocalyx degradation markers (heparan sulfate, soluble thrombomodulin, albumin), a potential “sheddase”: Matrix Metalloproinase 9 (MMP9) and neutrophil activation/tissue damage (neutrophil gelatinase-associated lipocalin, NGAL) in patient plasma from 44 HFRS patients collected consecutively following disease onset. We used the generalized estimating equation to analyse the association between endothelial glycocalyx degradation, MMP9 levels, neutrophil activation/tissue damage and HFRS disease outcome (need for oxygen, transfusion with blood components, need for intensive care unit (ICU) treatment and renal damage).Results: 44 HFRS patients were included in this study (29 females (66%)); need for oxygen: 11 (25%); transfusion with blood components: 3 (7%) and stay at ICU: 2 (5%)). The levels of MMP9 were significantly associated with all markers of endothelial glycocalyx degradation. Neutrophil activation/tissue damage (NGAL) was also significantly associated with MMP9 and endothelial glycocalyx degradation markers (apart from albumin (p = 0.053). In addition degradation of endothelial glycocalyx associated with HFRS disease outcome.Conclusion: Degradation of the endothelial glycocalyx could be a potential mechanism of HFRS pathogenesis, and potentially MMP9 could contribute to degradation of the endothelial glycocalyx
  •  
41.
  • Rasmussen, Marianne N. P., et al. (författare)
  • Permanent Distal Occlusion of Middle Cerebral Artery in Rat Causes Local Increased ETB, 5-HT1B and AT(1) Receptor-Mediated Contractility Downstream of Occlusion
  • 2013
  • Ingår i: Journal of Vascular Research. - : S. Karger AG. - 1423-0135 .- 1018-1172. ; 50:5, s. 396-409
  • Tidskriftsartikel (refereegranskat)abstract
    • Background/Aims: In response to experimental stroke, a characteristic functional and expressional upregulation of contractile G-protein-coupled receptors has been uncovered in the affected cerebral vasculature; however, the mechanism initiating this phenomenon remains unknown. Methods: Using a model of permanent distal occlusion of rat middle cerebral arteries, we investigated whether there was a regional difference in receptor-mediated contractility of segments located upstream and downstream of the occlusion site. The contractile response to endothelin, angiotensin and 5-hydroxytryptamine receptor stimulation was studied by sensitive wire myograph. Results: Only downstream segments exhibited an augmented contractile response to stimulation with each of the three ligands, with the response towards sarafotoxin 6c being especially augmented compared to sham, upstream and contralateral controls. This functional increase did not seem to relate to ischemic tissue damage, inflammatory cell infiltration or the element of reperfusion. Interestingly, immunohistochemistry did not show any difference in the level of immunoreactivity towards endothelin B (ETB) receptors between groups. Conclusion: Single artery occlusion without significant visible infarct resulted in locally increased ETB, angiotensin type 1 and 5-hydroxytryptamine 1B receptor-mediated contractile responses only in segments located downstream of the occlusion site. This suggests lack of wall stress as an initiating trigger leading to regulation of contractile response after cerebral stroke. (C) 2013 S. Karger AG, Basel
  •  
42.
  • Rippe, Bengt, et al. (författare)
  • Transendothelial transport: the vesicle controversy.
  • 2002
  • Ingår i: Journal of Vascular Research. - : S. Karger AG. - 1423-0135 .- 1018-1172. ; 39:5, s. 375-390
  • Forskningsöversikt (refereegranskat)abstract
    • The relative contribution of transcytosis vs. large pore transport to the passage of macromolecules across microvascular endothelia has been a controversial issue for nearly half a century. To separate transcytosis from 'porous' transport, the transcytosis inhibitors N-ethylmaleimide (NEM) and filipin have been tested in in situ or ex vivo perfused organs with highly conflicting results. In continually weighed isolated perfused organs, where measurements of pre- and post-capillary resistances, capillary pressure and capillary filtration coefficients can be repeatedly performed, high doses of NEM and filipin increased the bulk transport of macromolecules from blood to tissue, despite producing vasoconstriction. By contrast, in in situ perfused organs, marked reductions in the tissue uptake of albumin tracer have been observed after NEM and filipin. When tissue cooling has been employed as a means of inhibiting (active) transcytosis, results have invariably shown a low cooling sensitivity of albumin transport, compatible with passive transendothelial passage of albumin. This observation is further strengthened by the commonly observed dependence of albumin transport upon the capillary pressure and the rate of transcapillary convection. For low-density lipoprotein (LDL), a cooling-sensitive, non-selective transport component has been discovered, which may be represented by filtration through paracellular gaps, lateral diffusion through transendothelial channels formed by fused vesicles, or by transcytosis. From a physiological standpoint there is little evidence supporting active transendothelial transport of most plasma macromolecules. This seems to be supported by studies on caveolin-1-deficient mice lacking plasmalemmal vesicles (caveolae), in which there are no obvious abnormalities in the transendothelial transport of albumin, immunoglobulins or lipoproteins. Nevertheless, specific transport in peripheral capillaries of several hormones and other specific substances, similar to that existing across the blood-brain barrier, still remains as a possibility.
  •  
43.
  • Rosengren, Bert-Inge, et al. (författare)
  • Transendothelial transport of low-density lipoprotein and albumin across the rat peritoneum in vivo: Effects of the transcytosis inhibitors NEM and filipin
  • 2002
  • Ingår i: Journal of Vascular Research. - : S. Karger AG. - 1423-0135 .- 1018-1172. ; 39:3, s. 230-237
  • Tidskriftsartikel (refereegranskat)abstract
    • This study was performed to investigate the mechanisms responsible for the transport of albumin and low-density lipoprotein (LDL) across capillary walls in vivo. To separate transcytosis from passive, 'porous' transport, we tested the effects of the transcytosis inhibitors N-ethylmaleimide (NEM) and filipin given intraperitoneally on the peritoneal capillary clearance of LDL and albumin in anesthetized rats undergoing peritoneal dialysis. Radiolabeled human albumin or LDL was given intraarterially, and Cr-51-EDTA was infused intravenously. A 2-hour peritoneal dialysis dwell was performed using 16 ml of conventional 1.36% glucose-based dialysis fluid. The clearance of LDL and albumin to the dialysate and the peritoneal mass transfer coefficient for Cr-51-EDTA were assessed. Following intraperitoneal NEM incubations (0.5-5 mM), there were marked increases in the peritoneal transport of albumin and LDL for NEM doses exceeding 1 mM. For lower NEM doses, there were no reductions in clearance. Filipin incubations (0.24 ug/ml) did not affect the clearance of either macromolecule. In conclusion, neither NEM nor filipin caused reductions in albumin or LDL clearance across the peritoneal capillaries. The present data clearly show that NEM and filipin are unsuitable as transcytosis inhibitors in vivo. Copyright (C) 2002 S. Karger AG, Basel.
  •  
44.
  • Rosengren, Bert-Inge, et al. (författare)
  • Transvascular Passage of Macromolecules into the Peritoneal Cavity of Normo- and Hypothermic Rats in vivo: Active or Passive Transport?
  • 2004
  • Ingår i: Journal of Vascular Research. - : S. Karger AG. - 1423-0135 .- 1018-1172. ; 41:2, s. 123-130
  • Tidskriftsartikel (refereegranskat)abstract
    • During the last decades there has been a debate regarding whether transvascular protein transport is an active (transcytosis) or a passive (porous) process. To separate cooling-sensitive transcytosis from passive transport processes between blood and peritoneal fluid, we induced hypothermia in rats in vivo, reducing their body temperature to 19°C. Control rats were kept at 37°C. Either human albumin, or IgG, or IgM, or LDL, radiolabeled with <sup>125</sup>I, was given intra-arterially together with <sup>51</sup>Cr-EDTA. During tracer administration, a 2-hour peritoneal dialysis dwell was performed. Clearance of the tracers to dialysate, and the permeability-surface area coefficient (PS) for <sup>51</sup>Cr-EDTA and glucose were assessed. During cooling, mean arterial blood pressure (MAP) was reduced to 40% of control and plasma viscosity increased by 48.5%, while peritoneal blood flow was reduced to 10%. At 19°C, clearance of albumin to dialysate fell from 9.30 ± 1.62 (SEM) to 3.13 ± 0.28 µl/min (p < 0.05), clearance of IgG from 6.33 ± 0.42 to 2.54 ± 0.12 µl/min (p < 0.05), clearance of IgM from 3.65 ± 0.33 to 1.10 ± 0.12 µl/min (p < 0.05), and clearance of LDL from 3.54 ± 0.20 to 0.73 ± 0.06 µl/min (p < 0.05). The fall in PS for <sup>51</sup>Cr-EDTA was from 0.320 ± 0.01 to 0.075 ± 0.003 ml/min (p < 0.05), and that for glucose from 0.438 ± 0.02 to 0.105 ± 0.01 ml/min (p < 0.05). Tissue cooling reduced large solute transport largely in proportion to the cooling-induced reductions of MAP (to 40%), and the concomitant increase in viscosity (to 67%), i.e. to &#8776;20–30% (0.40 × 0.67) of control, though LDL clearance was reduced further. The fall in small solute PS, in excess of the viscosity effect, mirrored the fall in peritoneal blood flow occurring during hypothermia. In conclusion, the good correlation of predicted to calculated changes suggests that the overall transendothelial macromolecular passage in vivo occurs passively, and not due to active processes.
  •  
45.
  • Rousseau, Andreas, et al. (författare)
  • Prostaglandins and Radical Oxygen Species Are Involved in Microvascular Effects of Hyperoxia
  • 2010
  • Ingår i: JOURNAL OF VASCULAR RESEARCH. - : S. Karger AG. - 1018-1172 .- 1423-0135. ; 47:5, s. 441-450
  • Tidskriftsartikel (refereegranskat)abstract
    • Hyperoxia causes vasoconstriction in most tissues, by mechanisms that are not fully understood. We investigated microvascular effects of breathing 100% oxygen in healthy volunteers, using iontophoresis to deliver acetylcholine (ACh) and sodium nitroprusside (SNP). Aspirin and vitamin C were used to test for involvement of prostaglandins and radical oxygen species. Forearm skin perfusion was measured using laser Doppler perfusion imaging. Results were analysed using dose-response modelling. The response to ACh was reduced by 30% during oxygen breathing compared to air breathing [0.98 (0.81-1.15) PU vs. 1.45 (1.30-1.60) PU, p andlt; 0.001]. ED50 values were unchanged [2.25 (1.84-2.75) vs. 2.21 (1.79-2.74), not significant]. Aspirin pre-treatment abolished the difference in response between oxygen breathing and air breathing [maximum: 1.03 (0.90-1.16) vs. 0.89 (0.77-1.01), not significant; ED50: 1.83 (1.46-2.30) vs. 1.95 (1.65-2.30), not significant]. ACh-mediated vasodilatation during 100% oxygen breathing was partially restored after pre-treatment with vitamin C. Breathing 100% oxygen did not change the microvascular response to SNP [1.45 (1.28-1.62) vs. 1.40 (1.26-1.53), not significant]. These results favour the hypothesis that hyperoxic vasoconstriction is mediated by inhibition of prostaglandin synthesis. Radical oxygen species may be involved as vitamin C, independently of aspirin, partially restored ACh-mediated vasodilatation during hyperoxia.
  •  
46.
  • Sangha, GS, et al. (författare)
  • Effects of Iliac Stenosis on Abdominal Aortic Aneurysm Formation in Mice and Humans
  • 2019
  • Ingår i: Journal of vascular research. - : S. Karger AG. - 1423-0135 .- 1018-1172. ; 56:5, s. 217-229
  • Tidskriftsartikel (refereegranskat)abstract
    • Reduced lower-limb blood flow has been shown to lead to asymmetrical abdominal aortic aneurysms (AAAs) but the mechanism of action is not fully understood. Therefore, small animal ultrasound (Vevo2100, FUJIFILM VisualSonics) was used to longitudinally study mice that underwent standard porcine pancreatic elastase (PPE) infusion (<i>n</i> = 5), and PPE infusion with modified 20% iliac artery stenosis in the left (<i>n</i> = 4) and right (<i>n</i> = 5) iliac arteries. Human AAA computed tomography images were obtained from patients with normal (<i>n</i> = 9) or stenosed left (<i>n</i> = 2), right (<i>n</i> = 1), and bilateral (<i>n</i> = 1) iliac arteries. We observed rapid early growth and rightward expansion (8/9 mice) in the modified PPE groups (<i>p</i> &#x3c; 0.05), leading to slightly larger and asymmetric AAAs compared to the standard PPE group. Further examination showed a significant increase in TGFβ1 (<i>p</i> &#x3c; 0.05) and cellular infiltration (<i>p</i> &#x3c; 0.05) in the modified PPE group versus standard PPE mice. Congruent, yet variable, observations were made in human AAA patients with reduced iliac outflow compared to those with normal iliac outflow. Our results suggest that arterial stenosis at the time of aneurysm induction leads to faster AAA growth with aneurysm asymmetry and increased vascular inflammation after 8 weeks, indicating that moderate iliac stenosis may have upstream effects on AAA progression.
  •  
47.
  • Sarabi, Mahziar, et al. (författare)
  • Relationships between Endothelium-Dependent Vasodilation, Serum Vitamin E and Plasma Isoprostane 8-Iso-PGF2alpha Levels in Healthy Subjects
  • 1999
  • Ingår i: Journal of Vascular Research. - : S. Karger AG. - 1018-1172 .- 1423-0135. ; 36:6, s. 486-491
  • Tidskriftsartikel (refereegranskat)abstract
    • Due to the reported associations between a low intake of vitamin E and atherosclerosis on one hand, and between endothelial dysfunction and atherosclerosis on the other hand, we investigated the relationship between endothelium-dependent vasodilation and serum levels of vitamin E (alpha- and gamma-tocopherol) as well as the lipid peroxidation markers malondialdehyde and 8-iso-PGF(2alpha) in a healthy population. Healthy subjects (31 men and 25 women), aged between 20 and 69 years, underwent measurements of forearm blood flow (FBF) at rest and during local infusion of 2 and 4 microg/min of methacholine (Mch, to evaluate endothelium-dependent vasodilation) and 5 and 10 microg/min of sodium nitroprusside (SNP, to evaluate endothelium-independent vasodilation, and during reactive hyperemia using venous occlusion plethysmography. Serum alpha-tocopherol concentration was significantly related to the index of endothelial function (r = 0.46, p < 0.01), defined as the ratio between the maximal dilatations during Mch and SNP infusions. Serum gamma-tocopherol levels were positively related to the maximal FBF during reactive hyperemia (r = 0.54, p < 0.01) in women only. Furthermore, in women only, plasma 8-iso-PGF(2alpha) levels were inversely related to the relative increases in FBF during both Mch and SNP infusions (r = -0.58 and r = -0.59, p < 0.01 for both). The results show a relationship between the levels of alpha-tocopherol and endothelial vasodilatory function, suggesting a beneficial role for this potent lipid-soluble antioxidant also in a population sample of apparently healthy subjects. Furthermore, in women, the accumulation of lipid peroxidation products such as 8-iso-PGF(2alpha) seems to be associated with an impaired vasodilation in general.
  •  
48.
  • Schonherr, E, et al. (författare)
  • Decorin deficiency leads to impaired angiogenesis in injured mouse cornea
  • 2004
  • Ingår i: Journal of Vascular Research. - : S. Karger AG. - 1423-0135 .- 1018-1172. ; 41:6, s. 499-508
  • Tidskriftsartikel (refereegranskat)abstract
    • Small leucine-rich proteoglycans play important roles in the organization of the extracellular matrix as well as for the regulation of cell behavior; two biological processes that are essential for angiogenesis. We investigated consequences of the targeted ablation of decorin (DCN), biglycan (BGN) and fibromodulin (FMOD) genes on inflammation-induced angiogenesis in the cornea. In wildtype mice, DCN was localized exclusively to the corneal stroma, while FMOD and BGN were more prominently expressed in epithelial cells. Endothelial cells from limbus blood vessels expressed BGN and FMOD, but no DCN. However, after induction of angiogenesis by chemical cauterization, DCN was expressed in the newly formed capillaries, together with BGN and FMOD. Notably, in DCN-deficient mice, the growth of vessels was significantly diminished, whereas it did not significantly change in FMOD- or BGN-deficient animals. Moreover, blood vessels of DCN-deficient mice exhibited a similar expression level of BGN as control mice, while FMOD was increased on day 3 after injury. These results indicate that DCN, in addition to its effects on fibrillogenesis, plays a regulatory role in angiogenesis and that FMOD in endothelial cells may be able to partially substitute for DCN.
  •  
49.
  • Settergren, M, et al. (författare)
  • Endothelin-A receptor blockade increases nutritive skin capillary circulation in patients with type 2 diabetes and microangiopathy
  • 2008
  • Ingår i: Journal of vascular research. - : S. Karger AG. - 1423-0135 .- 1018-1172. ; 45:4, s. 295-302
  • Tidskriftsartikel (refereegranskat)abstract
    • <i>Aims:</i> Endothelin-1 levels are elevated in patients with type 2 diabetes mellitus and may contribute to impaired microvascular function. We investigated the effect of selective endothelin-A (ET<sub>A</sub>) receptor blockade (BQ123) on skin microcirculation in patients with type 2 diabetes and albuminuria. <i>Methods:</i> Ten type 2 diabetes patients and 8 non-diabetic controls were investigated. Nutritive skin capillary circulation, investigated by videophotometric capillaroscopy, and total skin microcirculation, assessed by laser Doppler fluxmetry (LDF), were studied during intra-arterial infusion of saline for 15 min, followed by BQ123 infusion for 60 min. <i>Results:</i> Following BQ123 infusion there was a significant increase in resting capillary blood cell velocity (CBV) in patients with type 2 diabetes from 0.24 (0.20–0.34) mm/s at baseline to 0.61 (0.46–0.88) mm/s at 60 min, but no significant change in the control subjects [0.55 (0.10–0.68) vs. 0.38 (0.13–0.88) mm/s; p < 0.005 for difference between groups]. Peak CBV following arterial occlusion and skin temperature increased significantly in the type 2 diabetes group but not in the control group during BQ123 infusion. There were no significant changes in LDF parameters during infusion of BQ123 in either group. <i>Conclusion:</i> ET<sub>A</sub> receptor blockade improves nutritive skin capillary circulation in patients with type 2 diabetes and microangiopathy.
  •  
50.
  • Smedby, Örjan, et al. (författare)
  • Two-dimensional tortuosity of the superficial femoral artery in early atherosclerosis.
  • 1993
  • Ingår i: Journal of Vascular Research. - : S. Karger AG. - 1018-1172 .- 1423-0135. ; 30:4, s. 181-191
  • Tidskriftsartikel (refereegranskat)abstract
    • Tortuosity of an artery can disturb fluid mechanics and cause flow separation, which might in turn promote atherogenesis. This study discusses theoretically several quantitative measures of arterial tortuosity and curvature in two dimensions and tests them with computations from digitized femoral arteriograms. When reproducibility, sensitivity to scaling and computational procedure, and agreement between the measures were all taken into account, the total curvature and distance factor were considered the most suitable measures. Significant correlations were found between tortuosity and atherosclerosis measures, but the interpretation of this finding is not straightforward.
  •  
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