[Suppression of the exaggerated growth of vascular smooth muscle cells from SHR by antisense oligodeoxynucleotide to TGF beta]

Abstract

Faster growth is observed in cultured vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR) compared to cells from normotensive Wistar Kyoto (WKY) rats. It has been reported that transforming growth factor-beta (TGF beta), a bifunctional growth factor, shows higher mRNA accumulation in VSMC from SHR. Antisense oligodeoxynucleotide (ODN) complementary to TGF beta 1 mRNA significantly suppressed DNA synthesis of VSMC from SHR at high cell density in a dose-dependent manner, but elicited little inhibition of VSMC from WKY rats. Antisense ODN resulted in a depression of the cell number increase in SHR VSMC only. While DNA synthesis of VSMC was inhibited by antisense ODN at high cell density, it was stimulated at low cell density in both strains. In the presence of antisense ODN, plasmin, an activator of TGF beta, was unable to stimulate DNA synthesis of VSMC. These findings implicate a role of endogenous TGF beta in the exaggerated growth of VSMC from SHR.