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Gene Transfer for Ischemic Heart Failure in a Preclinical Model
Published on: May 15, 2011
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Postinfarction treatment with an adenoviral vector expressing hepatocyte growth factor relieves chronic left
Yiwen Li1, Genzou Takemura, Ken-ichiro Kosai
1Second Department of Internal Medicine, Gifu University School of Medicine, 40 Tsukasa-Machi, Gifu 500-8705, Japan.
Circulation
|April 16, 2003
Summary
Hepatocyte growth factor (HGF) gene therapy improved heart function after myocardial infarction by promoting cardiomyocyte growth and reducing fibrosis. This offers a new treatment strategy for postinfarction heart failure.
Area of Science:
- Cardiovascular Biology
- Regenerative Medicine
- Gene Therapy
Background:
- Hepatocyte growth factor (HGF) plays roles in tissue regeneration, angiogenesis, and anti-apoptosis.
- The chronic effects of HGF on post-myocardial infarction (MI) left ventricular (LV) remodeling and heart failure remain unclear.
Purpose of the Study:
- To investigate the therapeutic potential of HGF gene therapy in mitigating adverse LV remodeling and dysfunction following myocardial infarction.
Main Methods:
- Adenovirus-mediated delivery of human HGF (Ad.CAG-HGF) to hindlimb muscles in a mouse model of MI.
- Assessment of LV remodeling, function, infarct size, cardiomyocyte hypertrophy, fibrosis, and cell proliferation/apoptosis at 4 weeks post-MI.
Main Results:
- HGF-treated mice exhibited improved LV remodeling and function, characterized by smaller LV cavity, reduced heart/body weight ratio, enhanced fractional shortening, and lower LV end-diastolic pressure.
- Increased cardiomyocyte hypertrophy, thicker infarct walls with greater vascular density, and significantly reduced ventricular fibrosis were observed in HGF-treated mice.
- While infarct size was similar, HGF therapy augmented c-Met/HGF receptor expression and promoted granulation tissue cell proliferation with reduced apoptosis near the infarct zone.
Conclusions:
- Postinfarction HGF gene therapy effectively improved LV remodeling and cardiac function.
- Therapeutic benefits were attributed to cardiomyocyte hypertrophy, infarct wall thickening, preserved vasculature, and antifibrotic effects.
- These findings suggest HGF gene therapy as a promising novel approach for treating postinfarction heart failure.
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