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

Mol Biol Rep. 2010 Apr;37(4):1957-69. doi: 10.1007/s11033-009-9642-z. Epub 2009 Aug 4.

Abstract

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 microl 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-beta1, 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics*
  • Animals
  • Blotting, Western
  • Cell Movement
  • Cell Survival
  • Chemokine CXCL12 / genetics
  • Chemokine CXCL12 / metabolism
  • Chemokine CXCL12 / therapeutic use*
  • Endomyocardial Fibrosis / complications*
  • Endomyocardial Fibrosis / pathology
  • Endomyocardial Fibrosis / physiopathology
  • Endomyocardial Fibrosis / therapy
  • Fluorescent Antibody Technique
  • Gene Expression Regulation
  • Heart Function Tests
  • Hemodynamics
  • Humans
  • Leukocyte Count
  • Leukocytes, Mononuclear / cytology
  • Myocardial Infarction / genetics
  • Myocardial Infarction / pathology
  • Myocardial Infarction / physiopathology*
  • Myocardial Infarction / therapy*
  • Myocardium / pathology*
  • Myocytes, Cardiac / pathology
  • Neovascularization, Pathologic / complications*
  • Neovascularization, Pathologic / pathology
  • Neovascularization, Pathologic / physiopathology
  • Neovascularization, Pathologic / therapy
  • Rats
  • Rats, Wistar
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stem Cells / cytology

Substances

  • Chemokine CXCL12