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 expression vector harboring the cDNA for PGI(2) synthase (PGIS), which catalyzes the rearrangement of prostaglandin H-2 to PGI(2). Transfection of the human PGIS cDNA into rat VSMC did not affect DNA synthesis under serum free basal conditions, but it increased PGI(2) synthesis and decreased DNA synthesis under serum-stimulated conditions (in the presence of 1 or 5% fetal calf serum). These results demonstrated that locally 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 such as neointimal hyperplasia. (C) 1995 Academic Press, Inc.