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 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.


CONCLUSIONS
SDF-1 alpha could improve cardiac structure and function after Myocardial infarction through angiogenic and anti-fibrotic actions.
Tang
Junming
J
Institute of Clinical Medicine, Renmin Hospital, Yunyang Medical College, 442000, Shiyan, Hubei, People's Republic of China. tangjm416@163.com
Wang
Jianing
J
Song
Hongxian
H
Huang
Yongzhang
Y
Yang
Jianye
J
Kong
Xia
X
Guo
Linyun
L
Zheng
Fei
F
Zhang
Lei
L
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D015153:Blotting, Western; D002465:Cell Movement; D002470:Cell Survival; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D004719:Endomyocardial Fibrosis / Q000150:complications* / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation; D006334:Heart Function Tests; D006439:Hemodynamics; D006801:Humans; D007958:Leukocyte Count; D007963:Leukocytes, Mononuclear / Q000166:cytology; D009203:Myocardial Infarction / Q000235:genetics / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy*; D009206:Myocardium / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000150:complications* / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology
D054377:Chemokine CXCL12