ANTISENSE INHIBITION OF BASIC FIBROBLAST GROWTH-FACTOR INDUCES APOPTOSIS IN VASCULAR SMOOTH-MUSCLE CELLS

Basic fibroblast growth factor (bFGF), a potent mitogen for many cell types, is expressed by vascular smooth muscle cells and plays a promin ent role in the proliferative response to vascular injury. Basic FGF h as also been implicated as a survival factor for a variety of quiescen t or terminally differentiated cells. Autocrine mechanisms could poten tially mediate both proliferation and cell survival. To probe such aut ocrine pathways, endogenous bFGF production was inhibited in cultured rat vascular smooth muscle cells by the expression of antisense bFGF R NA. Inhibition of endogenous bFGF production induced apoptosis in thes e cells independent of proliferation, and apoptosis could be prevented by exogenous bFGF but not serum or epidermal growth factor. The induc tion of apoptosis was associated with an inappropriate entry into S ph ase. These data demonstrate that interruption of autocrine bFGF signal ing results in apoptosis of vascular smooth muscle cells, and that the mechanism involves disruption of normal cell cycle regulation.