Autocrine-paracrine effects of overexpression of hepatocyte growth factor gene on growth of endothelial cells.

Although hepatocyte growth factor (HGF) is synthesized in vascular cells, it is not known whether locally synthesized HGF acts similarly to exogenously added HGF. Therefore, we transfected cultured cells with human HGF vector and examined the effects on growth of vascular cells. Endothelial cells (EC) transfected with HGF vector synthesized and secreted high levels of HGF, and also showed significantly higher number. Addition of conditioned medium from vascular smooth muscle cells (VSMC) or EC transfected with HGF vector to nontransfected EC resulted in a significant increase in cell number, which was abolished by anti-HGF antibody. Co-culture of HGF-transfected VSMC with EC showed that HGF released from VSMC or EC stimulated EC growth. These results demonstrate that endogenously produced HGF by transfection of human HGF vector can exert autocrine and paracrine stimulatory effects on EC growth, but not VSMC growth, suggesting the role of local HGF system in cardiovascular disease.