| 1. |
- Andersson, Maria, 1975, et al.
(author)
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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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In: J Vasc Res. - : S. Karger AG. - 1018-1172. ; 42:5, s. 441-52
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Journal article (peer-reviewed)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.
(author)
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Altered IL-32 Signaling in Abdominal Aortic Aneurysm
- 2020
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In: Journal of Vascular Research. - : KARGER. - 1018-1172 .- 1423-0135. ; 57:4, s. 236-244
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Journal article (peer-reviewed)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.
(author)
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Prostacyclin reduces microvascular fluid conductivity in cat skeletal muscle through opening of ATP-dependent potassium channels
- 1999
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In: Journal of Vascular Research. - 1423-0135. ; 36:6, s. 516-523
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Journal article (peer-reviewed)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
(author)
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New Frontiers in VEGF/VEGFR Biology
- 2015
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In: Journal of Vascular Research. - 1018-1172 .- 1423-0135. ; 52, s. 79-79
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Journal article (other academic/artistic)
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| 6. |
- Dahan, Diana, et al.
(author)
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MicroRNA-Dependent Control of Serotonin-Induced Pulmonary Arterial Contraction
- 2017
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In: Journal of Vascular Research. - : S. Karger AG. - 1018-1172 .- 1423-0135. ; 54:4, s. 246-256
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Journal article (peer-reviewed)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.
(author)
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Increased store-operated Ca2+ entry into contractile vascular smooth muscle following organ culture
- 2001
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In: Journal of Vascular Research. - : S. Karger AG. - 1423-0135 .- 1018-1172. ; 38:4, s. 324-331
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Journal article (peer-reviewed)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.
(author)
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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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In: Journal of vascular research. - : S. Karger AG. - 1423-0135 .- 1018-1172. ; 58:1, s. 58-64
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Journal article (other academic/artistic)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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| 10. |
- Emilsson, K, et al.
(author)
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Vascular effects of proteinase-activated receptor 2 agonist peptide
- 1997
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In: Journal of Vascular Research. - 1423-0135. ; 34:4, s. 267-272
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Journal article (peer-reviewed)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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