文章摘要
Zhengxian Tao,Bo Chen,Yingming Zhao,Hongwu Chen,Liansheng Wang,Yonghong Yong,Kejiang Cao,Qifeng Yu,Danian Ke,Hua Wang,Zuze Wu,Zhijian Yang.[J].南京医科大学学报,2010,(3):198~206
HGF percutaneous endocardial injection induces cardiomyocyte proliferation and rescues cardiac function in pigs
投稿时间:2010-05-10  
DOI:10.7655
中文关键词: 
英文关键词: HGF, EnSite NavX, cardiac function, gene therapy, proliferation, myocardial infarction
基金项目:
作者单位
Zhengxian Tao Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China 
Bo Chen Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China 
Yingming Zhao Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China 
Hongwu Chen Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China 
Liansheng Wang Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China 
Yonghong Yong Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China 
Kejiang Cao Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China 
Qifeng Yu MicroPort Medical (Shanghai) CO., Ltd., Shanghai 201203, China 
Danian Ke MicroPort Medical (Shanghai) CO., Ltd., Shanghai 201203, China 
Hua Wang Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing 100850, China 
Zuze Wu Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing 100850, China 
Zhijian Yang Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China 
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中文摘要:
      
英文摘要:
      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 CMI. Pigs were randomized (1:1:1) to receive adenoviral vector HGF (total dose, 1×1010 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 mapping. HGF and cyclin proteins were detected by western blot and immunoprecipitation analysis. Histological and immunohistochemical analysis determined proliferating cardiomyocytes. Myocardial 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 Ad-HGF. After treatment there were more proliferating cardiomyocytes in the HGF group compared to either of the control groups. Furthermore, the HGF group myocardial samples expressed higher levels of p-Akt, cyclin A, cyclin E, cyclin D1, cdk2, cdk4 than those in the control groups. Conclusion: The over-expression of HGF activates pro-survival pathways, induces cardiomyocyte proliferation, and improves the perfusion and function of the porcine CMI heart.
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