BACKGROUND: We hypothesized that transfection of the gene for human hepatocyte growth factor (hHGF) combined with cellular cardiomyoplasty might regenerate the impaired myocardium. METHODS AND RESULTS: We used a ligation model of proximal left anterior descending coronary artery (LAD) of Lewis rats. Two weeks after LAD ligation, 3 different treatments were conducted: (1) neonatal rat cardiomyocytes group (10(6) cells, T group, n=11), (2) HVJ-liposomes bearing the hHGF gene group (H group, n=10), and (3) combined (T-H group, n=10). The injection site was the scar area of myocardial infarction. For control, culture medium was injected (C group, n=13). Echocardiography demonstrated that cardiac performance was significantly ameliorated in the T-H group 4 and 8 weeks after injection. Contrast echocardiography also showed a marked increase in myocardial perfusion in the T-H group but not in the other groups. In the T-H group, neovascularization and a marked reduction of fibrosis were observed histologically. In an immunohistochemical study, strong staining for beta(1)-integrin, alpha-, and beta-dystroglycan were found principally in the basement membrane of myocytes in the T-H group 8 weeks after transplantation, although there was weak immunoreactivity in the T group. CONCLUSIONS: hHGF gene transfection enhanced the cellular cardiomyoplasty possibly by stimulating angiogenesis, restoring the impaired ECM, and promoting the integration of the dissociated grafted myocytes. The combined effects might have lead to the improved cardiac performance. Thus, combined therapy may be a promising strategy for the treatment of heart failure caused by myocardial infarction.
BACKGROUND: We hypothesized that transfection of the gene for humanhepatocyte growth factor (hHGF) combined with cellular cardiomyoplasty might regenerate the impaired myocardium. METHODS AND RESULTS: We used a ligation model of proximal left anterior descending coronary artery (LAD) of Lewis rats. Two weeks after LAD ligation, 3 different treatments were conducted: (1) neonatal rat cardiomyocytes group (10(6) cells, T group, n=11), (2) HVJ-liposomes bearing the hHGF gene group (H group, n=10), and (3) combined (T-H group, n=10). The injection site was the scar area of myocardial infarction. For control, culture medium was injected (C group, n=13). Echocardiography demonstrated that cardiac performance was significantly ameliorated in the T-H group 4 and 8 weeks after injection. Contrast echocardiography also showed a marked increase in myocardial perfusion in the T-H group but not in the other groups. In the T-H group, neovascularization and a marked reduction of fibrosis were observed histologically. In an immunohistochemical study, strong staining for beta(1)-integrin, alpha-, and beta-dystroglycan were found principally in the basement membrane of myocytes in the T-H group 8 weeks after transplantation, although there was weak immunoreactivity in the T group. CONCLUSIONS:hHGF gene transfection enhanced the cellular cardiomyoplasty possibly by stimulating angiogenesis, restoring the impaired ECM, and promoting the integration of the dissociated grafted myocytes. The combined effects might have lead to the improved cardiac performance. Thus, combined therapy may be a promising strategy for the treatment of heart failure caused by myocardial infarction.
Authors: Carmela Zincarelli; Stephen Soltys; Giuseppe Rengo; Walter J Koch; Joseph E Rabinowitz Journal: Clin Transl Sci Date: 2010-06 Impact factor: 4.689