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Angiogenesis and antifibrotic action by hepatocyte growth factor in cardiomyopathy
Yoshiaki Taniyama1, Ryuichi Morishita, Motokuni Aoki
1Department of Geriatric Medicine, Graduate School of Medicine, Osaka University, Suita 565-0871, Japan.
Insights
Hepatocyte growth factor (HGF) gene transfer improved cardiac function in cardiomyopathic hamsters by increasing blood flow and reducing fibrosis. This suggests HGF therapy may protect against heart muscle injury in cardiomyopathy.
Area of Science:
- Cardiology
- Molecular Biology
- Regenerative Medicine
Background:
- Cardiomyopathy impairs cardiac function due to reduced blood flow and increased collagen synthesis.
- Growth factors offer a potential therapeutic strategy to address fibrosis and blood flow issues in dilated cardiomyopathy.
Purpose of the Study:
- To investigate the therapeutic potential of hepatocyte growth factor (HGF) in treating cardiomyopathy.
- To examine the effects of HGF gene overexpression on fibrosis and microvascular dysfunction in a cardiomyopathic hamster model.
Main Methods:
- Hereditary cardiomyopathic Syrian hamsters (Bio 14.6) received weekly intra-cardiac injections of HGF gene or control vector.
- Treatment was administered from 12 to 20 weeks of age (8 total treatments).
- Echocardiography, laser Doppler imaging for blood flow, and alkaline phosphatase staining for capillary density were used for assessment.
Main Results:
- HGF gene transfection significantly increased cardiac blood flow (P<0.01).
- Capillary density in the heart was significantly enhanced in the HGF group (P<0.01).
- The fibrotic area within the myocardium was significantly reduced by HGF gene transfer (P<0.01).
Conclusions:
- In vivo HGF gene transfer promotes angiogenesis and reduces fibrosis in the myocardium.
- HGF gene therapy demonstrates cardioprotective effects, suggesting its potential utility in managing cardiomyopathy.
- HGF's antifibrosis and angiogenesis actions may offer a novel therapeutic approach for myocardial protection.
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.