Potential role of a novel vascular modulator, hepatocyte growth factor (HGF), in cardiovascular disease: characterization and regulation of local HGF system.

Abstract

Since endothelial cells (EC) are known to secrete various anti-proliferative and vasodilating factors, an agent that promotes seeding or regeneration of EC may have potential therapeutic value against vascular smooth muscle cell (VSMC) proliferation. To seek an endothelium specific growth factor, we have focused on hepatocyte growth factor (HGF). HGF is belonged to a member of endothelium specific growth factors, whose mitogenic action on EC was most potent among growth factors. Moreover, the presence of local HGF system (HGF and its specific receptor, c-met) was observed in EC and VSMC of rat and human in vitro as well as in vivo. Production of local HGF production in vascular cells was regulated by various cytokines including transforming growth factor (TGF)-beta and angiotensin II (Ang II). Furthermore, HGF may be a therapeutic growth factor for the treatment of restenosis after angioplasty and arteriosclerosis obliterance, etc., as gene therapy. From these characteristics of HGF, we hypothesized that HGF might contribute to the protection or repair of vascular endothelial cells. Indeed, serum HGF concentration was significantly correlated with blood pressure, suggesting that HGF secretion might be elevated in response to high blood pressure as a counter-system against endothelial dysfunction. In this review, we discussed that HGF is a member of the endothelium specific growth factors whose serum concentration is significantly associated with blood pressure.