on June 10, 2002
Published online before print June 10, 2002, doi: 10.1161/01.HYP.0000020755.56955.BF
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Submitted on February 21, 2002
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. * To whom correspondence should be addressed. E-mail: morishit{at}geriat.med.osaka-u.ac.jp.
Abstract—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.
Revised on March 22, 2002
Angiogenesis and Antifibrotic Action by
Hepatocyte Growth Factor in
Cardiomyopathy
Yoshiaki Taniyama;
Key words: cardiomyopathy • fibrosis • angiogenesis • gene therapy • hepatocyte growth factor
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