Vascular microarray profiling in two models of hypertension identifies caveolin-1, Rgs2 and Rgs5 as antihypertensive targetsReport as inadecuate




Vascular microarray profiling in two models of hypertension identifies caveolin-1, Rgs2 and Rgs5 as antihypertensive targets - Download this document for free, or read online. Document in PDF available to download.

BMC Genomics

, 8:404

First Online: 07 November 2007Received: 27 March 2007Accepted: 07 November 2007

Abstract

BackgroundHypertension is a complex disease with many contributory genetic and environmental factors. We aimed to identify common targets for therapy by gene expression profiling of a resistance artery taken from animals representing two different models of hypertension. We studied gene expression and morphology of a saphenous artery branch in normotensive WKY rats, spontaneously hypertensive rats SHR and adrenocorticotropic hormone ACTH-induced hypertensive rats.

ResultsDifferential remodeling of arteries occurred in SHR and ACTH-treated rats, involving changes in both smooth muscle and endothelium. Increased expression of smooth muscle cell growth promoters and decreased expression of growth suppressors confirmed smooth muscle cell proliferation in SHR but not in ACTH. Differential gene expression between arteries from the two hypertensive models extended to the renin-angiotensin system, MAP kinase pathways, mitochondrial activity, lipid metabolism, extracellular matrix and calcium handling. In contrast, arteries from both hypertensive models exhibited significant increases in caveolin-1 expression and decreases in the regulators of G-protein signalling, Rgs2 and Rgs5. Increased protein expression of caveolin-1 and increased incidence of caveolae was found in both smooth muscle and endothelial cells of arteries from both hypertensive models.

ConclusionWe conclude that the majority of differences in gene expression found in the saphenous artery taken from rats with two different forms of hypertension reflect distinctive morphological and physiological alterations. However, changes in common to caveolin-1 expression and G protein signalling, through attenuation of Rgs2 and Rgs5, may contribute to hypertension through augmentation of vasoconstrictor pathways and provide potential targets for common drug development.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2164-8-404 contains supplementary material, which is available to authorized users.

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Author: T Hilton Grayson - Stephen J Ohms - Therese D Brackenbury - Kate R Meaney - Kaiman Peng - Yvonne E Pittelkow - Susan R

Source: https://link.springer.com/article/10.1186/1471-2164-8-404







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