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HGF percutaneous endocardial injection induces cardiomyocyte proliferation and rescues cardiac function in pigs

The Journal of Biomedical Research 2010年第3期24卷 198-206页

作者： Zhengxian Tao Bo Chen Yingming Zhao Hongwu Chen Liansheng Wang Yonghong Yong Kejiang Cao Qifeng Yu Danian Ke` Hua Wang Zuze Wu Zhijian Yang Department of Cardiology the First Affiliated Hospital of Nanjing Medical University Nanjing 210029 Jiangsu Province China. MieroPort Medical (Shanghai) CO. Ltd. Shanghai 201203 China Department of Experimental Hematology Beijing Institute of Radiation Medicine Beijing 100850 China

Objective：To investigate the effect of cardiomyocyte proliferation induced by human hepatocyte growth factor（HGF）in pigs with chronic myocardial infarction（CMI）.Methods：A steerable,deflectable 7F catheter incorporating a 27-guage needle was advanced percutaneously to the left ventricular myocardium of 18 pigs with *** were randomized（1：1：1）to receive adenoviral vector HGF（total dose,1×10^10 genome copies）,which was administered as five injections into the infarcted myocardium（total,1.0 mL）,or saline,or Ad-null（control groups）.Injections were guided by ensite navx left ventricular electroanatomical *** and cyclin proteins were detected by western blot and immunoprecipitation *** and immunohistochemical analysis determined proliferating *** perfusion and cardiac function were estimated by Gated-Single Photon Emission Computed Tomography（G-SPECT）.Results：Western blot analyses showed that HGF were predominantly expressed in the infarct core and border in the myocardium of the infarcted heart.G-SPECT analysis indicated that the HGF group had better cardiac function and myocardial perfusion four weeks after the injection of Ad-HGF than before the injection of *** treatment there were more proliferating cardiomyocytes in the HGF group compared to either of the control ***,the HGF group myocardial samples expressed higher levels of p-Akt,cyclin A,cyclin E,cyclin D1,cdk2,cdk4 than those in the control ***：The over-expression of HGF activates pro-survival pathways,induces cardiomyocyte proliferation,and improves the perfusion and function of the porcine CMI heart.

关键词： HGF ensite navx cardiac function gene therapy proliferation myocardial infarction

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