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Ann Thorac Surg 2003;75:1283-1287
© 2003 The Society of Thoracic Surgeons

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Original article: cardiovascular

Gene transfer of hepatocyte growth factor improves angiogenesis and function of chronic ischemic myocardium in canine heart

^a First Department of Surgery, Osaka University Medical School, Osaka, Japan

Accepted for publication October 21, 2002.

^* Address reprint requests to Dr Sawa, First Department of Surgery, Osaka University Medical School, Yamada-oka 2-2, Suita, Osaka 565, Japan
e-mail: sawa{at}surg1.med.osaka-u.ac.jp

BACKGROUND: Hepatocyte growth factor (HGF) induces angiogenesis in myocardium. In the present study, its effects in chronic ischemic myocardium were tested.

METHODS: Four weeks after left anterior descending coronary artery ligation in canine hearts, HVJ-liposome containing either human HGF gene (160 µg; HGF group, n = 7) or nothing (control group, n = 6) was directly injected into ischemic myocardium. Four weeks after gene transfection, the thickness fraction (TF), an index of regional myocardial contractility (assessed by epicardial pulse-Doppler crystals), the myocardial perfusion flow (assessed by color microspheres), and the capillary density (assessed by immunostaining of vessels) were evaluated in ischemic myocardium.

RESULTS: Thickness fraction (percent of nonischemic myocardium) was significantly improved in the HGF group (80 ± 15 from 52 ± 16 of pregene; p < 0.05) whereas it was not changed in the control group (52 ± 10 from 50 ± 8 of pregene). The perfusion flow (% of nonischemic myocardium) was significantly improved in the HGF group (98 ± 17 from 51 ± 14 of pregene; p < 0.05) while it was not changed in the Control group (58 ± 13 from 62 ± 18 of pregene). The capillary density was significantly higher in the HGF group (894 ± 211/mm²; p < 0.05) than that in the control group (511 ± 127/mm²).

CONCLUSIONS: Gene transfection of HGF improved angiogenesis, thereby improved regional myocardial function and perfusion in chronic ischemic myocardium. It indicates a potent therapeutic value of HGF gene transfection for chronic ischemic heart diseases such as myocardial infarction.

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				Y. Cao, A. Hong, H. Schulten, and M. J. Post Update on therapeutic neovascularization Cardiovasc Res, February 15, 2005; 65(3): 639 - 648. [Abstract] [Full Text] [PDF]