BASIC FIBROBLAST GROWTH-FACTOR REGULATES EXTRACELLULAR-MATRIX AND CONTRACTILE PROTEIN EXPRESSION INDEPENDENT OF PROLIFERATION IN VASCULAR SMOOTH-MUSCLE CELLS

Basic fibroblast growth factor (bFGF) can influence proliferation and differentiation in vascular smooth muscle cells. Basic FGF promotes so me features of the synthetic phenotype (proliferation) but is known to inhibit others (collagen synthesis). Whether bFGF availability influe nces smooth muscle cell phenotype independent of proliferation is not known. The purpose of this study was to determine if the effects of bF GF on extracellular matrix and contractile protein expression are depe ndent on changes in proliferation. Basic FGF availability was manipula ted by adding bFGF to cultured cells or by inhibiting bFGF expression using antisense RNA, and adjusting culture conditions such that prolif eration was held constant. Compared to cells cultured in serum alone, smooth muscle a-actin and myosin heavy chain expression was markedly r educed by added bFGF, but was not influenced by antisense inhibition o f bFGF expression. Under the same conditions, collagen synthesis was i nhibited by added bFGF, and was stimulated by reduced bFGF expression. These consequences of altering bFGF availability were not associated with changes in FGF receptor expression. These findings demonstrate th at alterations in bFGF availability can regulate smooth muscle cell ph enotype independent of proliferation, which may be related to the regu lation of smooth muscle cell phenotype in vivo.