Vascular pharmacology
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Vascular pharmacology · Sep 2013
Alteration of endothelial proteoglycan and heparanase gene expression by high glucose, insulin and heparin.
Heparan sulfate proteoglycans (HSPGs) contain a core protein with glycosaminoglycans attached. Reduced glycosaminoglycan, in endothelial HSPGs syndecan and perlecan, is associated with diabetic cardiovascular complications but changes in core protein remain controversial. Since heparanase degrades heparan sulfate, we wished to determine if changes in endothelial heparanase mRNA, by high glucose (HG), correlate with changes in syndecan and perlecan core proteins, and to observe effects of heparin or insulin. ⋯ HG plus heparin and insulin increased heparanase and syndecan mRNA compared to all other treatments and decreased perlecan mRNA compared to control and HG alone. Heparin may protect endothelium from HG injury by reducing heparanase and increasing syndecan while insulin inhibits heparanase expression. Effects with insulin plus heparin suggest interference in transcriptional regulation of heparanase and syndecan genes.
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Vascular pharmacology · Mar 2013
Review Comparative Study'No-touch' saphenous vein harvesting improves graft performance in patients undergoing coronary artery bypass surgery: a journey from bedside to bench.
The saphenous vein is the most commonly used conduit in patients undergoing coronary artery bypass surgery yet its patency is inferior to the internal thoracic artery. Vascular damage inflicted to the vein when using conventional harvesting techniques affects its structure. Endothelial denudation is associated with early vein graft failure while damage of the outermost vessel layers has adverse long-term effects on graft performance. ⋯ A 'no-touch' technique, where the saphenous vein is removed with minimal trauma and normal architecture preserved, produces a superior graft with long term patency comparable to the internal thoracic artery. Interestingly, many experimental studies are aimed at repairing or replacing those regions of the saphenous vein damaged when harvesting conventionally. 'No-touch' harvesting is superior in coronary artery bypass patients with long-term data published 5years ago. Here we describe a 'bedside to bench' situation where the mechanisms underlying the improved performance of 'no touch' saphenous vein grafts in patients have been studied in the laboratory.
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Rho proteins, best known for their regulatory role in actin dynamics, stimulate a variety of processes important in the control of vascular function, including morphogenesis, migration, cell proliferation and adhesion, cell survival, gene expression, vesicle transport and microparticle formation. Rho GTPases have been implicated in several pulmonary vascular pathologies. Here we give an overview of the current knowledge of the role of Rho GTPases in vascular dysfunction, and pulmonary diseases such as pulmonary hypertension, pulmonary embolism, chronic obstructive pulmonary disease, acute lung injury and acute respiratory distress syndrome.
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Vascular pharmacology · Mar 2012
Metabotropic glutamate receptor 5 mediates phosphorylation of vascular endothelial cadherin and nuclear localization of β-catenin in response to homocysteine.
Elevated plasma homocysteine (Hcy) is an independent risk factor for vascular disease and stroke in part by causing generalized endothelial dysfunction. A receptor that is sensitive to Hcy and its intracellular signaling systems has not been identified. β-catenin is a pleiotropic regulator of transcription and cell function. Using a brain microvascular endothelial cell line (bEnd.3), we tested the hypothesis that Hcy causes receptor-dependent nuclear translocation of β-catenin. ⋯ Knockdown of mGluR5 expression with shRNA also rescued claudin-5 expression from the effects of Hcy treatment. These data uniquely identify mGluR5 as a master switch that drives β-catenin nuclear localization in vascular endothelium and regulates cell-cell coupling in response to elevated Hcy levels. These studies dissect a pharmacological opportunity for developing new therapeutic strategies in HHcy.