OVEREXPRESSION OF PROSTACYCLIN SYNTHASE INHIBITS GROWTH OF VASCULAR SMOOTH-MUSCLE CELLS

To define the local effects of prostacyclin (PGI(2)) on the growth of vascular smooth muscle cells (VSMC), we transfected VSMC with an expre ssion vector harboring the cDNA for PGI(2) synthase (PGIS), which cata lyzes the rearrangement of prostaglandin H-2 to PGI(2). Transfection o f the human PGIS cDNA into rat VSMC did not affect DNA synthesis under serum free basal conditions, but it increased PGI(2) synthesis and de creased DNA synthesis under serum-stimulated conditions (in the presen ce of 1 or 5% fetal calf serum). These results demonstrated that local ly synthesized PGI(2) can exert autocrine and/or paracrine inhibitory effects on VSMC growth. It was also suggested that in vivo transfer of PGIS gene may be useful for the gene therapy for vascular disease suc h as neointimal hyperplasia. (C) 1995 Academic Press, Inc.