Gene transfer of hepatocyte growth factor improves angiogenesis and function of chronic ischemic myocardium in canine heart

Background. Hepatocyte growth factor (HGF) induces angiogenesis in myocardium. In the present study, its effects in chronic ischemic myocardium were tested. Methods. Four weeks after left anterior descending coronary artery ligation in canine hearts, HVJ-liposome containing either human HGF gene (160 mug; HGF group, n = 7) or nothing (control group, n = 6) was directly injected into ischemic myocardium. Four weeks after gene transfection, the thickness fraction (TF), an index of regional myocardial contractility (assessed by epicardial pulse-Doppler crystals), the myocardial perfusion flow (assessed by color microspheres), and the capillary density (assessed by immunostaining of vessels) were evaluated in ischemic myocardium. Results. Thickness fraction (percent of nonischemic myocardium) was significantly improved in the HGF group (80 +/- 15 from 52 +/- 16 of pregene; p < 0.05) whereas it was not changed in the control group (52 +/- 10 from 50 +/- 8 of pregene). The perfusion flow (% of nonischemic myocardium) was significantly improved in the HGF group (98 +/- 17 from 51 +/- 14 of pregene; p < 0.05) while it was not changed in the Control group (58 +/- 13 from 62 +/- 18 of pregene). The capillary density was significantly higher in the HGF group (894 +/- 211/mm(2); p < 0.05) than that in the control group (511 +/- 127/mm(2)). Conclusions. Gene transfection of HGF improved angiogenesis, thereby improved regional myocardial function and perfusion in chronic ischemic myocardium. It indicates a potent therapeutic value of HGF gene transfection for chronic ischemic heart diseases such as myocardial infarction. (C) 2003 by The Society of Thoracic Surgeons.