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

Abstract

We tested the hypothesis that PKCβ contributes to vascular smooth muscle cell (SMC) migration and proliferation; processes central to the pathogenesis of restenosis consequent to vascular injury. Homozygous PKCβ null (−/−) mice or wild-type mice fed the PKCβ 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 PKCβII 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 PKCβ in the SMC response to acute arterial injury and suggest that blockade of PKCβ may represent a therapeutic strategy to limit restenosis.