Hepatocyte growth factor (HGF) angiogenic gene therapy: promises for cardiovascular diseases

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 was originally identified as a potent mitogen for hepatocytes, it has also been shown to be an angiogenic growth factor. Interestingly, the presence of its specific receptor, c-met, is observed in vascular cells and cardiac myocytes. In addition, among growth factors, the mitogenic action of HGF on human endothelial cells was most potent. Recent studies on animal models have demonstrated the potential application of HGF angiogenic gene therapy to treat cardiovascular diseases such as peripheral arterial disease (PAD), myocardial infarction, cerebrovascular disease and post-angioplastic restenosis. In this review, we present early results from an HGF gene therapy trial on six patients with PAD/Buerger disease and discuss the attractive promises of HGF gene transfer for cardiovascular diseases.