Vascular microarray profiling in two models of hypertension identifies caveolin-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.


CONCLUSIONS
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.
Grayson
T Hilton
TH
Division of Neuroscience, John Curtin School of Medical Research, Australian National University, Canberra, Australia. hilton.grayson@anu.edu.au
Ohms
Stephen J
SJ
Brackenbury
Therese D
TD
Meaney
Kate R
KR
Peng
Kaiman
K
Pittelkow
Yvonne E
YE
Wilson
Susan R
SR
Sandow
Shaun L
SL
Hill
Caryl E
CE
D000818:Animals; D001808:Blood Vessels / Q000378:metabolism*; D051242:Caveolin 1 / Q000235:genetics*; D020869:Gene Expression Profiling; D006973:Hypertension / Q000235:genetics*; D008957:Models, Genetic; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D020710:RGS Proteins / Q000235:genetics*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013045:Species Specificity
D051242:Caveolin 1; D020710:RGS Proteins; C514563:RGS2 protein, rat; C491348:Rgs5 protein, rat