Dataset Information

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

ABSTRACT:

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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.

SUBMITTER: Tang J

PROVIDER: S-EPMC2831180 | biostudies-literature | 2010 Apr

REPOSITORIES: biostudies-literature

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

Tang Junming J Wang Jianing J Song Hongxian H Huang Yongzhang Y Yang Jianye J Kong Xia X Guo Linyun L Zheng Fei F Zhang Lei L

Molecular biology reports 20090804 4

<h4>Unlabelled</h4>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 ...[more]

PMID: 19653123

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Project description:Microvascular malperfusion after myocardial infarction leads to infarct expansion, adverse remodeling, and functional impairment. Native reparative mechanisms exist but are inadequate to vascularize ischemic myocardium. We hypothesized that a 3-dimensional human fibroblast culture (3DFC) functions as a sustained source of angiogenic cytokines, thereby augmenting native angiogenesis and limiting adverse effects of myocardial ischemia.Lewis rats underwent ligation of the left anterior descending coronary artery to induce heart failure; experimental animals received a 3DFC scaffold to the ischemic region. Border-zone tissue was analyzed for the presence of human fibroblast surface protein, vascular endothelial growth factor, and hepatocyte growth factor. Cardiac function was assessed with echocardiography and pressure-volume conductance. Hearts underwent immunohistochemical analysis of angiogenesis by co-localization of platelet endothelial cell adhesion molecule and alpha smooth muscle actin and by digital analysis of ventricular geometry. Microvascular angiography was performed with fluorescein-labeled lectin to assess perfusion.Immunoblotting confirmed the presence of human fibroblast surface protein in rats receiving 3DFC, indicating survival of transplanted cells. Increased expression of vascular endothelial growth factor and hepatocyte growth factor in experimental rats confirmed elution by the 3DFC. Microvasculature expressing platelet endothelial cell adhesion molecule/alpha smooth muscle actin was increased in infarct and border-zone regions of rats receiving 3DFC. Microvascular perfusion was also improved in infarct and border-zone regions in these rats. Rats receiving 3DFC had increased wall thickness, smaller infarct area, and smaller infarct fraction. Echocardiography and pressure-volume measurements showed that cardiac function was preserved in these rats.Application of a bioengineered 3DFC augments native angiogenesis through delivery of angiogenic cytokines to ischemic myocardium. This yields improved microvascular perfusion, limits infarct progression and adverse remodeling, and improves ventricular function.

Dataset Information

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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Conclusion

Publications

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

Similar Datasets

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