Published online before print June 10, 2002, doi: 10.1161/01.HYP.0000020755.56955.BF
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(Hypertension. 2002;40:47.)
© 2002 American Heart Association, Inc.
Scientific Contributions |
Angiogenesis and Antifibrotic Action by Hepatocyte Growth Factor in Cardiomyopathy
From the Department of Geriatric Medicine (R.M., M.A., K.H., K.Y., N.H., T.O.), Division of Gene Therapy Science (R.M., Y.K.), and Division of Biochemistry, Department of Oncology, Biomedical Research Center (K.M., T.N.), Graduate School of Medicine, Osaka University, Suita 565-0871, Japan.
Correspondence to Ryuichi Morishita, MD, PhD, Associate Professor, Division of Gene Therapy Science, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita 565-0871, Japan. E-mail morishit{at}geriat.med.osaka-u.ac.jp
Impairment of cardiac function in cardiomyopathy has been postulated to be related to decreased blood blow and increased collagen synthesis. Therefore, a therapeutic approach to alter the blood flow or fibrosis directly by means of growth factors may open a new therapeutic concept in dilated cardiomyopathy. From this viewpoint, hepatocyte growth factor (HGF) is a unique growth factor with antifibrosis and angiogenesis effects. Using the hereditary cardiomyopathic Syrian hamster as a model of genetically determined cardiomyopathy and heart failure, the effects of overexpression of HGF on fibrosis and microvascular dysfunction were examined. HGF gene or control vector was injected by the Hemagglutinating Virus of Japan–liposome method into the anterior heart of cardiomyopathic hamsters (Bio 14.6) under echocardiography once a week, from 12 to 20 weeks of age (total, 8 times). Blood flow, as assessed by a laser Doppler imager score, and the capillary density in hearts, as assessed by alkaline phosphatase staining, were significantly increased in hamsters transfected with HGF gene compared with control-vector-transfected hamsters (P<0.01). In contrast, the fibrotic area was significantly decreased in hamsters transfected with HGF gene compared with control (P<0.01). Overall, in vivo experiments demonstrated that transfection of HGF gene into the myocardium of cardiomyopathic hamsters stimulated blood flow through the induction of angiogenesis and reduction of fibrosis. These results suggest that HGF gene transfer may be useful to protect against myocardial injury in cardiomyopathy through its cardioprotective effects such as antifibrosis and angiogenesis actions.
Key Words: cardiomyopathy • fibrosis • angiogenesis • gene therapy • hepatocyte growth factor
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