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Inhibition of cardiovascular cell proliferation by angiotensin receptor blockers: are all molecules the same?

Abstract：

BACKGROUND:Few studies have directly compared the effects of different angiotensin receptor blockers (ARBs) on mechanisms involved in the pathogenesis of cardiovascular disease. METHODS:We studied the ability of different ARBs to inhibit the proliferation of vascular smooth muscle cells (VSMCs) and cardiac fibroblasts (CFs) in continuous culture and in quiescent cells stimulated to proliferate by platelet-derived growth factor (PDGF) and insulin. We also investigated whether the antiproliferative effects of ARBs depended on their ability to block angiotensin II receptors or activate the peroxisome proliferator-activated receptor gamma (PPAR gamma). RESULTS:Dose-response studies showed that candesartan, eprosartan, and irbesartan had little or no effect on the proliferation of VSMC or CF in continuous culture even when tested at concentrations as high as 10 mumol/l or when tested in cells stimulated with PDGF/insulin. In contrast, telmisartan inhibited VSMC and CF proliferation by 50-70% (P < 0.05) in a dose-dependent and reversible fashion and significantly inhibited the increases in cyclin D1 levels and cell proliferation induced by PDGF/insulin. Antiproliferative effects of telmisartan were also observed in Chinese hamster ovary (CHO-K1) cells that lack functional angiotensin II receptors and in human VSMCs treated with the PPAR gamma antagonist GW9662. CONCLUSION:Telmisartan, but not candesartan, irbesartan, or eprosartan, can significantly inhibit the proliferation of VSMC and CF in culture when tested at concentrations near those that can be achieved in plasma with usual oral dosing. Telmisartan can also inhibit the proliferation of cells that lack angiotensin II receptors and cells treated with a PPAR gamma antagonist suggesting that the antiproliferative effects of telmisartan may involve more than just angiotensin II receptor blockade or activation of PPAR gamma.

journal_name

J Hypertens

journal_title

Journal of hypertension

authors

Benson SC,Iguchi R,Ho CI,Yamamoto K,Kurtz TW

doi

10.1097/HJH.0b013e3282f56ba5

subject

Has Abstract

pub_date

2008-05-01 00:00:00

pages

973-80

issue

eissn

0263-6352

issn

1473-5598

pii

00004872-200805000-00020

journal_volume

pub_type

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Inhibition of cardiovascular cell proliferation by angiotensin receptor blockers: are all molecules the same?