No abstract

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.

No abstract

Although the level of plasminogen activator (PA)

A significant fraction of the arterial smooth muscle cells in atherosclerotic plaques and injury-induced intimal thickenings express class II major histocompatibility complex (Ia) antigens. This might be the consequence of gamma-interferon secretion by T lymphocytes also present in these lesions. We have therefore analyzed the effects of gamma-interferon on cultured rat aortic smooth muscle cells. Recombinant gamma-interferon inhibited smooth muscle proliferation in vitro in a dose-response relation; inhibition was detectable down to a concentration of 1 unit/ml. In similar concentrations, gamma-interferon also induced Ia expression by the cells. This suggested that Ia antigens might be selectively expressed by nonproliferating smooth muscle cells. In vivo, there was a strong negative correlation between Ia expression and 3H-thymidine labeling of smooth muscle cells in intimal thickenings induced by balloon catheter injury. In rats receiving continuous infusions of 3H-thymidine for two weeks after injury, Ia-positive 3H-positive cells had undergone fewer rounds of replication than Ia-negative ones. This indicates that Ia-expression both in vivo and in vitro is associated with a reduced proliferative capacity. These results suggest that gamma-interferon, a secretory product of activated T lymphocytes, acts as a natural regulator of smooth muscle cell growth and Ia expression in injury-induced intimal thickenings and atherosclerotic plaques.