Suppression by heparin of smooth muscle cell proliferation in injured arteries.

Abstract

INTIMAL smooth muscle cell (SMC) proliferation dominates the early phase of healing after arterial endothelial injury1–6; what growth factors are responsible for this mitotic activity of an otherwise quiescent cell is not known. SMC growth in vitro is enhanced by platelet factors, insulin and lipoproteins7–11 and, according to some reports, can be diminished in vivo with various antiplatelet agents. Harker et al.6 have reported decreased myointimal thickening in homocystinaemic baboons treated with dipyridamole, and Friedman et al.11 and Moore et al.12 have reported suppression of SMC proliferation in the injured arteries of rabbits injected with anti-platelet serum. Intimal thickening was not diminished, however, in the injured carotid arteries of rats given various anti-platelet drugs13. Because the clotting system is inextricably linked to arterial injury and because thrombin is used to generate the platelet growth factor9 and may itself be a mitogen14,15, we speculated that heparin might inhibit myointimal thickening. We report here the use of heparin to suppress intimal SMC hyperplasia in a rat model of arterial endothelial injury and suggest possible mechanisms for the heparin effect.