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(Hypertension. 2006;48:664.)
© 2006 American Heart Association, Inc.

Original Articles

Angiotensin II Type 1 Receptor Blockade Attenuates In-Stent Restenosis by Inhibiting Inflammation and Progenitor Cells

Kisho Ohtani; Kensuke Egashira; Yoshiko Ihara; Kaku Nakano; Kouta Funakoshi; Gang Zhao; Masataka Sata; Kenji Sunagawa

From the Department of Cardiovascular Medicine (K.O., K.E., G.Z., Y.I., K.F., K.N., K.S.), Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; and the Department of Cardiovascular Medicine (M.S.), Graduate School of Medical Sciences, University of Tokyo, Tokyo, Japan.

Correspondence to Kensuke Egashira, Department of Cardiovascular Medicine Graduate School of Medical Science, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. E-mail egashira{at}cardiol.med.kyushu-u.ac.jp

The precise mechanism by which angiotensin II type 1 receptor blocker reduces in-stent restenosis in clinical trials is unclear. We, therefore, investigated the mechanism of in-stent neointima formation. Male cynomolgus monkeys and rabbits were fed a high-cholesterol diet and were allocated to untreated control and type 1 receptor blocker groups. Five days after grouping, multilink stents were implanted in the iliac artery. The type 1 receptor blocker reduced the development of in-stent neointima formation by 30% in rabbits and monkeys. To investigate potential mechanisms, we examined the expression of renin-angiotensin system markers, all of which increased in monocytes and smooth muscle-like cells in the neointima and media within 7 days. The type 1 receptor blocker attenuated increased oxidative stress, the enhanced expression of markers of the rennin-angiotensin system and monocyte chemoattractant protein-1, and macrophage infiltration. The effects of type 1 receptor blocker on the differentiation of peripheral blood mononuclear cells into vascular progenitor cells were also examined. Treatment with type 1 receptor blocker suppressed the enhanced differentiation to smooth muscle progenitor cells induced by stenting. The type 1 receptor blocker attenuated in-stent neointima formation by inhibiting redox-sensitive inflammatory changes and by reducing recruitment of the progenitor cells. These potential actions of type 1 receptor blocker on inflammation and progenitor cells constitute a novel mechanism of suppression of in-stent restenosis by type 1 receptor blocker.

Key Words: angiotensin II • oxidative stress • monocytes

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