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J Thorac Cardiovasc Surg 2005;130:295-302
© 2005 The American Association for Thoracic Surgery

Cardiopulmonary Support and Physiology

Reorganization of cytoskeletal proteins and prolonged life expectancy caused by hepatocyte growth factor in a hamster model of late-phase dilated cardiomyopathy

Haruhiko Kondoh, MD a , Yoshiki Sawa, MD a , Norihide Fukushima, MD a , Goro Matsumiya, MD a , Shigeru Miyagawa, MD a , Satoru Kitagawa-Sakakida, MD b , Imran A. Memon, MD a , Naomasa Kawaguchi, MD c , Nariaki Matsuura, MD c , Hikaru Matsuda, MD a , *

a Division of Cardiovascular Surgery, Department of Surgery, Osaka University Graduate School of Medicine, Osaka, Japan
b Department of Molecular Pharmacology, Osaka University Graduate School of Medicine, Osaka, Japan
c Department of Pathology, School of Allied Health Science, Faculty of Medicine, Osaka University Graduate School of Medicine, Osaka, Japan

Received for publication July 5, 2004; revisions received October 31, 2004; accepted for publication November 2, 2004.

* Address for reprints: Hikaru Matsuda, MD, Division of Cardiovascular Surgery, Department of Surgery, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan (Email: matsuda{at}surg1.med.osaka-u.ac.jp).

OBJECTIVE: It has been postulated recently that changes in cytoskeletal and sarcolemmal proteins initiate a final common pathway for contractile dysfunction in dilated cardiomyopathy. In ischemic cardiomyopathy, hepatocyte growth factor plays an important role in reorganizing the impaired cytoskeletal proteins in several cell types. We have tested the hypothesis that hepatocyte growth factor might improve life expectancy through modification of the molecular process that contributes to impairment in dilated cardiomyopathy.

METHODS: Adult male 27-week-old BIO TO-2 hamsters, which show moderate cardiac remodeling, were divided into treatment groups that received (1) hemagglutinating virus of Japan liposomes containing human hepatocyte growth factor cDNA (H group), (2) culture medium (C group), or (3) sham operation (S group).

RESULTS: After the operation, echocardiography demonstrated that the enlarged left ventricular end-systolic dimension and decreased fractional shortening were significantly attenuated in the H group compared with the C group. There was significantly less myocardial fibrosis in the H group compared with the C group. Immunohistochemical analysis showed alpha-dystroglycan and alpha- and beta-sarcoglycan expression in the basement membrane beneath the cardiomyocytes in the H group, whereas no expression of these proteins was seen in the C group. The 40-week survival was significantly better in the H group than in the C and S groups.

CONCLUSION: An improved survival associated with transient reorganization of the cytoskeletal proteins and reduction in myocardial fibrosis was achieved by hepatocyte growth factor treatment in an adult hamster model of dilated cardiomyopathy. The results suggest a therapeutic potential of hepatocyte growth factor in the treatment of dilated cardiomyopathy.




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