Kinetics of cellular proliferation after arterial injury. IV. Heparin inhibits rat smooth muscle mitogenesis and migration.

Heparin inhibits the development of intimal thickening after carotid injury in the rat; however, the specific cellular events responsible for this effect have not been defined. In this study, smooth muscle cell growth fraction and migration into the intima were quantitatively measured in heparin-treated animals. All rats were subjected to left carotid balloon injury and received continuous intraperitoneal infusion of tritiated thymidine; they were given either heparin or lactated Ringer's solution intravenously for periods of time up to 7 days. Both smooth muscle cell growth fraction and migration of nondividing smooth muscle cells were markedly reduced in heparin-treated rats. If heparin was administered for only the first 3 days after carotid injury, both smooth muscle growth fraction and migration were reduced at 7 days; on the other hand, heparin had no effect on growth fraction and migration if given from day 4 to day 7. Finally, heparin given for a period of 1 week produced marked reduction in smooth muscle cell accumulation in injured arteries at 2 and 4 weeks. These results suggest that the effect of heparin on injury-induced intimal thickening might be due to inhibition of both smooth muscle cell entry into the growth fraction and migration of medial smooth muscle cells into the intima. These effects are long lasting, and are not reversed even if heparin is stopped after a short course of administration.