Abstract
Aberrant vascular smooth muscle cell (VSMC) proliferation is the hallmark of both atherosclerosis and restenosis seen after vascular surgery. Heparin and heparan sulfate proteoglycans have been shown to inhibit VSMC proliferation in vitro and in vivo. Although the precise molecular mechanism of action of the atiproliferative effect of heparin is not yet understood, a number of studies have focused on: 1) binding of heparin to specific cell surface receptors and its subsequent internalization; 2) effects on cell cycle control machinery; 3) alteration of mitogenic signaling pathways; 4) regulation of gene expression, especially genes which encode proteins required for proliferation and genes encoding extracellular matrix proteins. In this review, we present an overview of the major contributions to understanding the antiproliferative mechanism of action of heparin.
