Adenovirus-mediated stromal cell-derived factor-1 alpha gene transfer improves cardiac structure and function after experimental myocardial infarction through angiogenic and antifibrotic actions |
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Authors: | Junming Tang Jianing Wang Hongxian Song Yongzhang Huang Jianye Yang Xia Kong Linyun Guo Fei Zheng Lei Zhang |
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Institution: | (1) Institute of Clinical Medicine, Renmin Hospital, Yunyang Medical College, 442000 Shiyan, Hubei, People’s Republic of China;(2) Department of Physiology, Yun Yang Medical College, 442000 Shiyan, Hubei, People’s Republic of China;(3) Key Lab of Human Embryonic Stem Cell of Hubei Province, Shiyan, Hubei, People’s Republic of China |
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Abstract: | Stromal cell-derived factor 1α (SDF-1) is not only a major chemotactic factor, but also an inducer of angiogenesis. The effects
of SDF-1α 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 × 1010 pfu/ml AdV-SDF-1 or 0.5 × 1010 pfu/ml Adv-LacZ were immediately injected into the infarcted myocardium, 120 μl 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/dtmax, 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-β1, TIMP-1 and TIMP-2 expression in AdV-SDF-1 group. Conclusion: SDF-1α could improve
cardiac structure and function after Myocardial infarction through angiogenic and anti-fibrotic actions. |
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