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(Circulation Research. 2005;96:476.)
© 2005 American Heart Association, Inc.

Molecular Medicine

Central Role of PKCß in Neointimal Expansion Triggered by Acute Arterial Injury

Martin Andrassy, Dmitry Belov, Evis Harja, Yu Shan Zou, Michael Leitges, Hugo A. Katus, Peter P. Nawroth, Shi Du Yan, Ann Marie Schmidt, Shi-Fang Yan

From the Departments of Surgery (M.A., D.B., E.H., Y.S.Z., A.M.S., S.-F.Y.) and Pathology (S.D.Y.), College of Physicians and Surgeons, Columbia University, New York; Max Planck Institute of Experimental Endocrinology (M.L.), Hannover, Germany; and the Departments of Cardiology (H.A.K.) and Medicine (P.P.N.), University of Heidelberg, Heidelberg, Germany.

Correspondence to Dr Shi-Fang Yan, Division of Surgical Science, Department of Surgery, College of Physicians and Surgeons of Columbia University, 630 West 168th St, New York, NY 10032. E-mail sy18{at}columbia.edu

We tested the hypothesis that PKCß contributes to vascular smooth muscle cell (SMC) migration and proliferation; processes central to the pathogenesis of restenosis consequent to vascular injury. Homozygous PKCß null (–/–) mice or wild-type mice fed the PKCß inhibitor, ruboxistaurin, displayed significantly decreased neointimal expansion in response to acute femoral artery endothelial denudation injury compared with controls. In vivo and in vitro analyses demonstrated that PKCßII is critically linked to SMC activation, at least in part via regulation of ERK1/2 MAP kinase and early growth response-1. These data highlight novel roles for PKCß in the SMC response to acute arterial injury and suggest that blockade of PKCß may represent a therapeutic strategy to limit restenosis.

Key Words: arterial injury • PKCß • smooth muscle cell activation • inhibitor • neointima

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