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3092 THERAPEUTIC ANGIOGENESIS USING HGF (HEPATOCYTE GROWTH FACTOR) GENE TO TREAT ISCHEMIC PERIPHERAL AND HEART DISEASE R Morishita, N Tomita, M Aoki, T Ogihara Osaka Univeisty, Suita, Japan Gene therapy is emerging as a potential strategy for the treatment of cardiovascular disease. Especially, most fruitful strategy is to stimulate blood vessel formation, so called angiogenesis. As we reported the potent angiogenic activity of hepatocyte growth factor (HGF), we planed a prospective open-labeled clinical trial of gene therapy (TREATHGF) by intramuscular injection of naked plasmid DNA in patients with PAD who had failed conventional therapy. A significant increase in ABI, reduction of resting and ulcer size was observed after gene therapy. Severe adverse effects related to gene transfer could not be detected in any patient. Currently, double-blinded placebo control phase III trial in Japan and phase II trial in USA are ongoing. Based on these data, the efficacy of therapeutic angiogenesis was evaluated in porcine chronic infarction model by direct injection of HGF into myocardium using needle injection catheter system. No animal had pericardial effusion or tamponade, and episodes of sustained ventricular arrhythmia after intramyocardial injection. At 1 month after injection, the ischemic area was significantly reduced by HGF gene therapy in a dose-dependent manner, accompanied by a significant increase in the ischemic territory blood supply. In addition to angiogenic property, we found that HGF has anti-fibrosis action through the blockade and degradation of collagen deposition, and anti-apoptotic action in cardiac myocytes. These favorable outcomes provide the potential utility to treat IHD patients using catheter-based, intramyocardial injection of HGF gene. Phase 1 study using HGF was started in 2004 in USA.