Contribution of a vascular modulator, hepatocyte growth factor (HGF), to the pathogenesis of cardiovascular disease.

HGF is a mesenchyme-derived pleiotropic factor which regulates cell growth, cell motility, and morphogenesis of various types of cells, and is thus considered a humoral mediator of epithelial-mesenchymal interactions responsible for morphogenic tissue interactions during embryonic development and organogenesis. Although HGF is originally identified as a most potent mitogen for hepatocytes, HGF is also belonged to a member of endothelium-specific growth factors. Since endothelial cells are known to secrete various anti-proliferative and vasodilating factors, an agent that promotes seeding or regeneration of endothelium may have potential therapeutic value against vascular smooth muscle cell proliferation. The mitogenic action of HGF on human endothelial cells was most potent among growth factors. Moreover, the presence of local HGF system (HGF and its specific receptor, c-met) was observed in vascular cells and cardiac myocytes 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 Ang II. Furthermore, HGF may be therapeutic growth factors for the treatment of restenosis after angioplasty and arteriosclerosis oblerance, etc., as gene therapy. On the other hand, serum HGF concentration was significantly correlated with blood pressure. These results suggest that HGF secretion might be elevated in response to high blood pressure as a counter-system against endothelial dysfunction, and may be considered as an index of severity of hypertension. In this review, we discussed the potential role of HGF in cardiovascular disease.