Recruitment of stem cells by hepatocyte growth factor via intracoronary gene transfection in the postinfarction heart failure

Abstract

We aim to study the amelioration effect of adenovirus5-mediated human hepatocyte growth factor gene transfer on postinfarction heart failure in swine model. Twelve Suzhong young swine were randomly divided into 2 groups of 6 pigs each: Ad(5)-HGF group and mock-vector Ad(5) group. Four weeks after ligation of the left anterior descending coronary artery, Ad(5)-HGF was intracoronarily transferred into the myocardium. Simultaneously, gate cardiac perfusion imaging was performed to evaluate the heart function. Three weeks later, gate cardiac perfusion imaging was performed again, then the hearts were removed and sectioned for immunohistochemical examination to illustrate the effects of Ad(5)-HGF on infarcted myocardium. The expression of HGF was examined by ELISA. The results were: (1) compared with the mock-vector Ad(5) group, high expression of human HGF was observed in the myocardium of Ad(5)-HGF group; (2) in the Ad(5)-HGF group, the number of CD117(+) cells co-expressing c-Met per mm(2) was significantly larger; (3) the improvement in LVEF was greater in the Ad(5)-HGF group than in the mock-vector Ad(5) group. We concluded that: (1) high expression of human HGF was observed in the myocardium through intracoronary gene transfection; (2) HGF can improve the mobilization of CD117(+)/c-Met(+) stem cells into ischemic myocardium. The amelioration effect of HGF on postinfarction heart failure could not be limited to stimulating angiogenesis, anti-apoptosis, anti-fibrosis, but was also involved in the recruitment of stem cells into myocardium.

Hepatocyte growth factor is a strong predictor of mortality in patients with advanced heart failure

“…Blockage of HGF by specific antibodies resulted in an increase of myocyte cell death. Additionally, HGF is thought to be involved in the recruitment of stem cells into ischaemic myocardium21 and to suppress oxidative stress 22. These cardioprotective effects were also associated with improvement of functional parameters such as perfusion and left ventricular function 4 6.…”

Cardiac Vasculature: Development and Pathology

“…(Lee et al, 2003;Su et al, 2002) and the treated animals have reduced infarct size and increased angiogenesis (Dong et al, 2009;Yockman et al, 2009). Hepatocyte growth factor gene therapy: Human Hepatocyte Growth Factor (hHGF) gene therapy induced angiogenesis in rats and dogs after experimental myocardial infarction (MI) and also improved cardiac function (Ahmet et al, 2002;Ahmet et al, 2003;Cho et al, 2008;Jayasankar et al, 2003;Jin et al, 2004;Li et al, 2003;Taniyama et al, 2002;Yang et al, 2007;Yang et al, 2010). HGF gene therapy combined with a novel gene transfection strategy that looks promising in a rat model of MI (Ahmet et al, 2003) is currently being evaluated in clinical trials.…”

Safety and Efficacy of Intracoronary Ad-HGF Administration for Treating Severe Coronary Disease: Results From Long-Term Follow-Up of a Phase I Clinical Trial

“…The written consents were obtained from all patients. Each patient received the optimal standardized medication therapy for coronary disease including aspirin or clopidogrel, beta blockers, statins, angiotensin conversion enzyme inhibitors or angiotensin II receptor blockers, and was treated with Ad-HGF only once (constructed and produced by Chinese Academy of Military Medical Sciences) [9][10][11][12]. Inclusion criteria for the intracoronary gene transfer were 50-80 years old with Canadian Cardiovascular Society class II to III angina, suffered from diffused and severe coronary disease confirmed by coronary angiography, the main coronaries not amenable to interventional therapy (angioplasty or stenting) or bypassing grafting, and no emergency revascularization during follow-ups.…”