| 1. |
- Andersson, Maria, 1975, et al.
(författare)
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Differential global gene expression response patterns of human endothelium exposed to shear stress and intraluminal pressure
- 2005
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Ingår i: J Vasc Res. - : S. Karger AG. - 1018-1172. ; 42:5, s. 441-52
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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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| 2. |
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| 3. |
- Bengts, Sophy, et al.
(författare)
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Altered IL-32 Signaling in Abdominal Aortic Aneurysm
- 2020
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Ingår i: Journal of Vascular Research. - : KARGER. - 1018-1172 .- 1423-0135. ; 57:4, s. 236-244
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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. |
- Claesson-Welsh, Lena
(författare)
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New Frontiers in VEGF/VEGFR Biology
- 2015
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Ingår i: Journal of Vascular Research. - 1018-1172 .- 1423-0135. ; 52, s. 79-79
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 5. |
- Dahan, Diana, et al.
(författare)
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MicroRNA-Dependent Control of Serotonin-Induced Pulmonary Arterial Contraction
- 2017
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Ingår i: Journal of Vascular Research. - : S. Karger AG. - 1018-1172 .- 1423-0135. ; 54:4, s. 246-256
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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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| 6. |
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| 7. |
- Dreja, Karl, et al.
(författare)
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Increased store-operated Ca2+ entry into contractile vascular smooth muscle following organ culture
- 2001
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Ingår i: Journal of Vascular Research. - : S. Karger AG. - 1423-0135 .- 1018-1172. ; 38:4, s. 324-331
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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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| 8. |
- Dull, RO, et al.
(författare)
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Syndecan-1 and Glypican-1 Knockout Alters Body Water Balance and Urine Response to Fluid Challenge in Mice
- 2021
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Ingår i: Journal of vascular research. - : S. Karger AG. - 1423-0135 .- 1018-1172. ; 58:1, s. 58-64
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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> < 0.05), higher excreted volume/infusion volume ratio (<i>p</i> < 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> < 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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| 9. |
- Eriksson, L, et al.
(författare)
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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
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Ingår i: Journal of vascular research. - : S. Karger AG. - 1423-0135 .- 1018-1172. ; 52:1, s. 41-52
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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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| 10. |
- Fogelstrand, Per, 1971, et al.
(författare)
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Increased Vascular Injury Reduces the Degree of Intimal Hyperplasia following Angioplasty in Rabbits.
- 2011
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Ingår i: Journal of vascular research. - : S. Karger AG. - 1423-0135 .- 1018-1172. ; 48:4, s. 307-15
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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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