Inhibition of smooth muscle cell proliferation in injured rat arteries. Interaction of heparin with basic fibroblast growth factor.

Abstract

Heparin inhibits smooth muscle cell (SMC) proliferation after arterial injury by mechanisms that have yet to be defined. Since the initiation of SMC proliferation is mediated by basic fibroblast growth factor (bFGF), we have investigated the possibility that heparin inhibits SMC proliferation by displacing bFGF from the arterial wall. Using a rat carotid artery model of balloon catheter injury, we demonstrate that a bolus injection of heparin depletes the arterial wall of both systemically administered bFGF and of endogenous bFGF. Heparin, however, does not reduce the bFGF content of unmanipulated arteries. Further, a single injection of heparin given at the time of balloon injury reduces SMC proliferation by 55% but has no effect when given 6 h after injury. SMC proliferation induced in a denuded artery by injection of bFGF is inhibited almost completely by a bolus injection of heparin; however, pretreatment with a bolus of heparin does not prevent SMC from responding to a subsequent bolus of bFGF. These experiments suggest that heparin can inhibit SMC proliferation in part by removal of released bFGF from sites of injury.