Vascular microarray profiling in two models of hypertension identifies Cav-1, Rgs2 and Rgs5 as antihypertensive targets

BACKGROUND: Hypertension 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. RESULTS: Differential 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. CONCLUSION: We 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

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

Abstract Background Hypertension 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. Results Differential 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. Conclusion We 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.</p

Vascular microarray profiling in two models of hypertension identifies caveolin-1, Rgs2 and Rgs5 as antihypertensive targets-3

<p><b>Copyright information:</b></p><p>Taken from "Vascular microarray profiling in two models of hypertension identifies caveolin-1, Rgs2 and Rgs5 as antihypertensive targets"</p><p>http://www.biomedcentral.com/1471-2164/8/404</p><p>BMC Genomics 2007;8():404-404.</p><p>Published online 7 Nov 2007</p><p>PMCID:PMC2219888.</p><p></p>aveolin-1 in both endothelial cells (EC: A-C) and in smooth muscle cells (SMC: D-F) of saphenous arteries taken from SHR (B, E) and ACTH (C, F), compared to WKY (A, D). Arrows indicate staining delineating the membranes of smooth muscle cells (D-F). Preincubation of the antibody with the immunogen eliminated staining in both endothelium and smooth muscle (G). Calibration bars represent 25 μm

Vascular microarray profiling in two models of hypertension identifies caveolin-1, Rgs2 and Rgs5 as antihypertensive targets-5

<p><b>Copyright information:</b></p><p>Taken from "Vascular microarray profiling in two models of hypertension identifies caveolin-1, Rgs2 and Rgs5 as antihypertensive targets"</p><p>http://www.biomedcentral.com/1471-2164/8/404</p><p>BMC Genomics 2007;8():404-404.</p><p>Published online 7 Nov 2007</p><p>PMCID:PMC2219888.</p><p></p>10 μm

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

<p><b>Copyright information:</b></p><p>Taken from "Vascular microarray profiling in two models of hypertension identifies caveolin-1, Rgs2 and Rgs5 as antihypertensive targets"</p><p>http://www.biomedcentral.com/1471-2164/8/404</p><p>BMC Genomics 2007;8():404-404.</p><p>Published online 7 Nov 2007</p><p>PMCID:PMC2219888.</p><p></p>he position of each array is shown as a label joined by a dotted line to the origin. B. A heat map (white: up-regulated; red: down-regulated) using hierarchical clustering with complete linkage for the columns only. The rank order of the p-values, gene names and Affymetrix IDs are included on the right and correspond to the numbering in A