Inhibitory effects of a novel antiatheromatous agent, E5050, on aortic smooth muscle cell proliferation, in vitro.

The effect of a novel antiatheromatous agent, N-(3-[4'-(2'',6''-dimethylheptyl)phenyl]butanoyl)ethanolamin e (E5050), on the proliferation of porcine aortic smooth muscle cells was studied in vitro. E5050 dose-dependently inhibited DNA synthesis as well as proliferation of cells stimulated with 10% fetal calf serum with no cytotoxic effects. An inhibitory effect of E5050 on DNA synthesis was also confirmed in cells stimulated with human platelet extract and with a combination of platelet-derived growth factor and human plasma-derived serum. DNA synthesis in smooth muscle cells stimulated with other mitogens, such as fibroblast growth factor and insulin, was inhibited by E5050 and this inhibitory effect was positively correlated with the E5050 uptake into smooth muscle cells. These results indicate that E5050 inhibits smooth muscle cell proliferation stimulated by various mitogenic factors. It is suggested that E5050 prevents atherogenesis and inhibits the progression of fibromuscular lesions by interfering with the proliferation of arterial smooth muscle cells.