Circulation. 2002;105:2556-2561
Published online before print April 15, 2002, doi: 10.1161/01.CIR.0000016722.37138.F2
Published online before print April 15, 2002, doi: 10.1161/01.CIR.0000016722.37138.F2
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(Circulation. 2002;105:2556.)
© 2002 American Heart Association, Inc.
Basic Science Reports |
Myocardial Regeneration Therapy for Heart Failure
Hepatocyte Growth Factor Enhances the Effect of Cellular Cardiomyoplasty
From the Division of Cardiovascular Surgery, Department of Surgery E1 (S.M., Y.S., S.T., H.M.), the Division of Biochemistry, Department of Oncology, Biomedical Research Center B7 (T.N.), and the Department of Pathology (N.K., N.M.), School of Allied Health Science, Faculty of Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.
Correspondence to Yoshiki Sawa, MD, Dept of Surgery, Osaka University Graduate School of Medicine E1, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan. E-mail sawa{at}surg1.med.osaka-u.ac.jp
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 (106 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 ß1-integrin, 
-, and ß-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.
Key Words: cells • heart failure • angiogenesis • cell adhesion molecules • transplantation
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