Gene therapy with hepatocyte growth factor for angiogenesis in severe pulmonary vascular disease

Severe pulmonary vascular disease, such as pulmonary hypertension (PH) which is characterized by proliferation of pulmonary artery smooth muscle cells and progression of pulmonary arterial fibrosis, is not curable without lung transplantation. Thus further development of alternative therapies is required. This article, using rat and piglet model of advanced pulmonary vascular diseases, shows that gene transfer with Hepatocyte Growth Factor (HGF) inhibited overgrowth of pulmonary artery smooth muscle cells and reduced lung expression level of endothelin-1 and TGF-beta, which prevented vascular medial hyperplasia and matrix accumulation of pulmonary arteries, as well as induced angiogenesis. HGF gene transfer also enhanced the ameliorating effect of PGIS in experimental PH. These results suggest that gene transfer with HGF may be found suitable in treating subjects with severe pulmonary vascular disease.