AUTOCRINE PARACRINE EFFECTS OF OVEREXPRESSION OF HEPATOCYTE GROWTH-FACTOR GENE ON GROWTH OF ENDOTHELIAL-CELLS

Although hepatocyte growth factor (HGF) is synthesized in vascular cel ls, it is not known whether locally synthesized HGF acts similarly to exogenously added HGF. Therefore, we transfected cultured cells with h uman HGF vector and examined the effects on growth of vascular cells. Endothelial cells (EC) transfected with HGF vector synthesized and sec reted high levels of HGF, and also showed significantly higher number. Addition of conditioned medium from vascular smooth muscle cells (VSM G) or EC transfected with HGF vector to nontransfected EG resulted in a significant increase in cell number, which was abolished by anti-HGF antibody. Go-culture of HGF-transfected VSMG with EG showed that HGF released from VSMG or EC stimulated EG growth. These results demonstra te that endogenously produced HGF by transfection of human HGF vector can exert autocrine and pancrine stimulatory effects on EG growth, but not VSMC growth, suggesting the role of local HGF system in cardiovas cular disease. (C) 1996 Academic Press, Inc.