Adenovirus-mediated stromal cell-derived factor-1 alpha gene transfer improves cardiac structure and function after experimental myocardial infarction through angiogenic and antifibrotic actions

Stromal cell-derived factor 1 alpha (SDF-1) is not only a major chemotactic factor, but also an inducer of angiogenesis. The effects of SDF-1 alpha on the left ventricular remodeling in a rat myocardial infarction (MI) model were analyzed. Myocardial infarction was induced by ligation of the left coronary artery in rats. 0.5 x 10(10) pfu/ml AdV-SDF-1 or 0.5 x 10(10) pfu/ml Adv-LacZ were immediately injected into the infarcted myocardium, 120 mu l cell-free PBS were injected into the infarcted region or the myocardial wall in control, and sham group, respectively. We found that AdV-SDF-1 group had higher LVSP and +/- dP/dt(max), lower LVEDP compared to control or Adv-LacZ group. The number of c-Kit(+) stem cells, and gene expression of SDF-1, VEGF and bFGF were obviously increased, which was associated with reduced infarct size, thicker left ventricle wall, greater vascular density and cardiocytes density in infarcted hearts of AdV-SDF-1 group. Furthermore, the expression of collagen type I and type III mRNA, and collagen accumulation in the infarcted area was lower, which was associated with decreased TGF-beta 1, TIMP-1 and TIMP-2 expression in AdV-SDF-1 group. Conclusion: SDF-1 alpha could improve cardiac structure and function after Myocardial infarction through angiogenic and anti-fibrotic actions.