Gene Therapy with Hepatocyte Growth Factor Improves Left Ventricular Systolic Function After Myocardial Infarction: A Systematic Review and Meta-analysis of Pig Models

Abstract

Background: Hepatocyte growth factor (HGF) is an angiogenic cytokine which can promote angiogenesis and inhibit fibrosis. Previous studies have shown that HGF may have significant therapeutic effects on ischaemic diseases, such as ischaemic heart disease and peripheral arterial occlusive disease. Due to insufficient clinical study evidence, we conducted a quantitative meta-analysis of HGF therapy in pigs with myocardial infarction (MI) to provide more reliable evidence for the feasibility and effectiveness of HGF therapy for MI patients. We also analysed the efficacy and characteristics of different gene therapy vectors and drug delivery routes.Methods: PubMed, EMBASE, and the China National Knowledge Infrastructure were searched for randomised studies that corresponded to our subject. The search terms included (hepatocyte growth factor OR HGF) AND (heart failure OR HF OR myocardial infarction OR MI OR AMI OR coronary heart disease OR CHD). The retrieved articles were screened strictly according to the inclusion criteria. The endpoints were the left ventricular ejection fraction (LVEF) and capillary density in the ischaemic regions in the model pigs.Results: A total of nine studies were eventually included in this meta-analysis. Our analysis showed that LVEF (with mean difference [MD]:9.73, 95%CI :8.70, 10.76, P < 0.00001) and capillary density (MD:79.98, 95%CI :24.58,135.39, P=0.005) in the HGF group were significantly higher than those in the control group several weeks after HGF treatment. Further analysis showed that there was no statistically significant difference in the improvement of LVEF caused by intracoronary adenovirus5-mediated HGF (Ad5-HGF) gene transfer and intramyocardial plasmid HGF injection (12.63±3.2 vs 9.4±1.09, P=0.06), while intramyocardial injection of plasmid HGF had a stronger angiogenic capacity than intramyocardial administration of Ad5-HGF and HGF in hydrogel (117.34±27.82 vs 26.45±22.11 vs 11.50±5.28, P＜0.00001).Conclusions: HGF therapy can effectively promote angiogenesis and recovery of cardiac function and is a promising cardiac repair method. Intracoronary Ad5 vector transfer and intramyocardial injection of plasmid vectors can be used as effective means of gene therapy, and hydrogel as a vector also has potential applications.