Exogenous basic fibroblast growth factor promotes cardiac stem cell-mediated myocardial regeneration after miniswine acute myocardial infarction

Abstract

To investigate the effects of exogenous basic fibroblast growth factor (bFGF) on myocardial regeneration after acute myocardial infarction (AMI). AMI models were established by ligating the mid-third of left anterior descending artery, thereafter, miniswines were randomly divided into control (none treatment, n = 6) and bFGF groups (n = 6). For the bFGF group, bFGF (100 μg) was injected with a sterile microinjection at five sites within the ischemic region. 5-Bromo-2-deoxyuridine (250 mg) was administrated intravenously twice a week after the operation, to label cells undergoing DNA replication. The expression of stromal cell-derived factor-1α (SDF-1α) and CXC chemokine receptor 4 (CXCR4), cardiac stem cell-mediated myocardial regeneration, myocardial apoptosis, histological and immunohistochemical analyses, and cardiac function were evaluated at different time points. Four weeks after bFGF therapy, it showed an increased vessel density and myocardial perfusion (P < 0.001), upregulative expression of SDF-1α and CXCR4 (P < 0.001), increased c-kit and 5-bromo-2-deoxyuridine-positive cells (P < 0.001), enhanced myocardial viability (P < 0.001), and improved left ventricular ejection fraction (P = 0.007), compared with the control. Exogenous bFGF was shown to have increased angiogenesis and myocardial perfusion, promoted myocardial regeneration by activating the SDF-1α/CXCR4 axis, and thereby improved the cardiac function, which may provide a new therapeutic strategy for AMI.