The inhibitory effect of a novel antiatheromatous agent, E5050, on the intimal thickening of aorta in cholesterol-fed rabbit in vivo.

ABSTRACT

The development of atheromatous lesions in the aortic arch of 0.5% cholesterol-fed rabbits was biochemically and morphologically examined. The animals were killed at week twelve (Cont-12W) or sixteen (Cont-16W). Both the micrographic and biochemical studies showed that the main atheromatous lesions in the Cont-12W group were fatty streaks, whereas those in the Cont-16W group were fibrous plaques. In these models, oral ingestion of 0.2% and 0.4% E5050, which has an antiproliferative effect on smooth muscle cells, had no effect on the surface involvement or the lipid content of the aortic arch at the sixteenth week, but reduced the degree of intimal thickening and the DNA content in the aortic arch in a dose-dependent manner. These results strongly suggest that E5050 suppresses the intimal thickening through its inhibitory effect on the proliferation of smooth muscle cells.