Hepatocyte growth factor gene transfer improves cardiac function and remodeling via enhancing angiogenesis and bcl-2 expression and decreasing hydroxyl radicals

• Published in: Journal of cardiac failure 2004-10, Vol.10 (5), p.S190-S190
• Main Authors: Xuehai, Chen, Shinya, Minatoguchi, Ningyuan, Wang, Chuanjiang, Lu, Masazumi, Arai, Yoshihiro, Uno, Kentaro, Yuge, Kenichiro, Kosai, Takako, Fujiwara, Hisayoshi, Fujiwara
• Format: Article
• Language: English
• ISSN: 1071-9164; 1532-8414
• DOI: 10.1016/j.cardfail.2004.08.141

Background: Gene transfer of hepatocyte growth factor (HGF) is reported to protect the heart against ischemia- reperfusion injury. However, its precise mechanisms are unknown. Methods: In male Japanese white rabbits, 1 × 10 9 particles of adenovirus Ad-HGF (HGF group, n = 15) or adenovirus Ad-LacZ (control group, n = 15) was directly injected into the myocardium. Three days after viral infection, the coronary artery was occluded for 30 min and reperfused. The heart was excised at 2 or 14 days after infarction. The infarct size and cardiac function were obtained. Bcl-2 protein was detected. Myocardial interstitial 2,5-DHBA levels, an indicator of hydroxyl radicals, were also measured. Results: The infarct size was significantly reduced in the HGF group (13.4 ± 2.3 %) than in the control group (36.5 ± 2.0 %) at 2 days after infarction. Smaller LV dimension and increased LV ejection fraction and higher capillary density assessed by immunostaining of CD31 were observed in the HGF group at 14-days after infarction. Bcl-2 protein was significantly increased at 4 h of reperfusion in the HGF group than in the control group. The 2,5-DHBA levels during ischemia and reperfusion was significantly attenuated in the HGF group compared to the control group. Conclusion: In vivo adenovirus-mediated HGF gene transfer improves cardiac function and remodeling via enhancing angiogenesis and Bcl-2 expression and decreasing hydroxyl radicals in a rabbit model of myocardial infarction.