Treatment of chronical myocardial ischemia by adenovirus-mediated hepatocyte growth factor gene transfer in minipigs

Growth factor gene transfer-induced therapeutic angiogenesis has become a novel approach for the treatment of myocardial ischemia. In order to provide a basis for the clinical application of an adenovirus with hepatocyte growth factor gene (Ad-HGF) in the treatment of myocardial ischemia, we establi...

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Bibliographic Details
Published in:Science China. Life sciences 2008-06, Vol.51 (6), p.537-543
Main Authors: Yuan, Biao, Zhang, YouRong, Zhao, Zhong, Wu, DanLi, Yuan, LiZhen, Wu, Bin, Wang, LiSheng, Huang, Jun
Format: Article
Language:English
Subjects:
Adenoviridae - genetics
Adenovirus
Adenoviruses
Angiogenesis
Animals
Biomedical and Life Sciences
Blood vessels
Coronary artery
Echocardiography
Female
Gene therapy
Genetic Therapy
Genetic Vectors
Growth factors
Heart
Hepatocyte growth factor
Hepatocyte Growth Factor - genetics
HGF gene
Ischemia
Life Sciences
Male
Myocardial ischemia
Myocardial Ischemia - diagnostic imaging
Myocardial Ischemia - therapy
Myocardium
Swine
Swine, Miniature
Tomography, Emission-Computed, Single-Photon
Ventricle
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Summary:Growth factor gene transfer-induced therapeutic angiogenesis has become a novel approach for the treatment of myocardial ischemia. In order to provide a basis for the clinical application of an adenovirus with hepatocyte growth factor gene (Ad-HGF) in the treatment of myocardial ischemia, we established a minipig model of chronically ischemic myocardium in which an Ameroid constrictor was placed around the left circumflex branch of the coronary artery (LCX). A total of 18 minipigs were randomly divided into 3 groups: a surgery control group, a model group and an Ad-HGF treatment group implanted with Ameroid constrictor. Ad-HGF or the control agent was injected directly into the ischemic myocardium, and an improvement in heart function and blood supply were evaluated. The results showed that myocardial perfusion remarkably improved in the Ad-HGF group compared with that in both the control and model groups. Four weeks after the treatment, the density of newly formed blood vessels was higher and the number of collateral blood vessels was greater in the Ad-HGF group than in the model group. The area of myocardial ischemia reduced evidently and the left ventricular ejection fraction improved significantly in the Ad-HGF group. These results suggest that HGF gene therapy may become a novel approach in the treatment of chronically ischemic myocardium.
ISSN:1006-9305
1674-7305
1862-2798
1869-1889
DOI:10.1007/s11427-008-0073-1