PLASMINOGEN-ACTIVATOR EXPRESSION IN RAT ARTERIAL SMOOTH-MUSCLE CELLS DEPENDS ON THEIR PHENOTYPE AND IS MODULATED BY CYTOKINES

Cultured rat aortic smooth muscle cells (SMCs) exhibit at least 2 phen otypic variants: (1) a spindle-shaped phenotype, obtained from normal adult media, and (2) an epithelioid phenotype, obtained from intimal t hickening 15 days after endothelial injury. Both phenotypes can be clo ned from each location, with normal media yielding a majority of spind le-shaped clones and intimal thickening yielding a majority of epithel ioid clones. These findings suggest that intimal thickening develops e ssentially from a subpopulation of medial SMCs exhibiting epithelioid features in vitro. Using zymographic and Northern blot analyses, we ha ve studied plasminogen activator (PA) expression by these SMCs. Our re sults show that epithelioid SMCs, cultured as whole SMC populations or as clones, display higher PA activity than do spindle-shaped SMCs, ir respective of their origin. This is mainly due to differences in the e xpression of tissue PA and, to a lesser extent, urokinase PA and is ac companied by a decrease in PA inhibitor 1. Tissue PA activity is incre ased by basic fibroblast growth factor and platelet-derived growth fac tor-BB, particularly in epithelioid SMCs. Taken together, these result s indicate that SMCs are heterogeneous with respect to their proteolyt ic profile, at least as far as the PA system is concerned. Proteolytic activity of the different SMC populations is modulated by cytokines t hat play a role in intimal thickening. Our results are in agreement wi th the suggestion that epithelioid SMCs are mainly responsible for int imal thickening.