MULTIPLE GROWTH-FACTORS ARE RELEASED FROM MECHANICALLY INJURED VASCULAR SMOOTH-MUSCLE CELLS

Local release of mitogenic and chemotactic signals during angioplasty- induced vascular injury may initiate restenosis. We investigated wheth er mechanical injury to vascular smooth muscle cells (VSMC) results in the release of biologically active peptide growth factors. Monolayers of bovine SMC cultures were mechanically injured by cell scraping. Co nditioned medium (CM) from control and injured SMC cultures was collec ted, and the mitogenic activity was measured by [H-3]thymidine incorpo ration in recipient SMC cultures. Mitogenic activity from injured CM w as detected within 15 min after injury. When the CM from injured cells was removed 15 min after injury and replaced with serum-free media, t here was no detectabe mitogenic activity in the replacement CM assesse d 1-6 days postinjury. Suramin, a nonspecific peptide growth factor an tagonist, significantly inhibited the mitogenic activity of injured CM . Basic fibroblast growth factor (bFGF), platelet-derived growth facto r (PDGF A chain), and epidermal growth factor (EGF) were detected in C M from injured cells by immunoblot analysis. The mitogenic activity of injured CM was significantly inhibited with neutralizing antibodies t o bFGF (34%), PDGF-AA (32%), PDGF-BB (25%), and EGF (25%). A neutraliz ing antibody to tranforming growth factor (TGF)-beta had no effect. In conclusion, bFGF, PDGF, and EGF are immediately released from mechani cally injured VSMC. VSMC Likely contain preformed, biologically active growth factors that are efficiently released from the cell cytoplasm following mechanical injury. Conditioned medium from injured VSMC is h ighly mitogenic, and this activity is probably due to multiple growth factors interacting synergistically.