|VEGF/SDF-1 promotes cardiac stem cell mobilization and myocardial repair in the infarcted heart.|
|PMID: 21345805 Owner: NLM Status: MEDLINE|
|AIMS: The objective of this study was to investigate whether vascular endothelial growth factor (VEGF) secreted by mesenchymal stem cells (MSC) improves myocardial survival and the engraftment of implanted MSC in infarcted hearts and promotes recruitment of stem cells through paracrine release of myocardial stromal cell-derived factor-1α (SDF-1α).
METHODS AND RESULTS: VEGF-expressing MSC ((VEGF)MSC)-conditioned medium enhanced SDF-1α expression in heart slices and H9C2 cardiomyoblast cells via VEGF and the vascular endothelial growth factor receptor (VEGFR). The (VEGF)MSC-conditioned medium markedly promoted cardiac stem cell (CSC) migration at least in part via the SDF-1α/CXCR4 pathway and involved binding to VEGFR-1 and VEGFR-3. In vivo, (VEGF)MSC-stimulated SDF-1α expression in infarcted hearts resulted in massive mobilization and homing of bone marrow stem cells and CSC. Moreover, VEGF-induced SDF-1α guided the exogenously introduced CSC in the atrioventricular groove to migrate to the infarcted area, leading to a reduction in infarct size. Functional studies showed that (VEGF)MSC transplantation stimulated extensive angiomyogenesis in infarcted hearts as indicated by the expression of cardiac troponin T, CD31, and von Willebrand factor and improved the left ventricular performance, whereas blockade of SDF-1α or its receptor by RNAi or antagonist significantly diminished the beneficial effects of (VEGF)MSC.
CONCLUSION: Exogenously expressed VEGF promotes myocardial repair at least in part through SDF-1α/CXCR4-mediated recruitment of CSC.
|Jun-Ming Tang; Jia-Ning Wang; Lei Zhang; Fei Zheng; Jian-Ye Yang; Xia Kong; Lin-Yun Guo; Long Chen; Yong-Zhang Huang; Yu Wan; Shi-You Chen|
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|Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2011-02-22|
|Title: Cardiovascular research Volume: 91 ISSN: 1755-3245 ISO Abbreviation: Cardiovasc. Res. Publication Date: 2011 Aug|
|Created Date: 2011-07-20 Completed Date: 2011-11-23 Revised Date: 2014-09-19|
Medline Journal Info:
|Nlm Unique ID: 0077427 Medline TA: Cardiovasc Res Country: England|
|Languages: eng Pagination: 402-11 Citation Subset: IM|
|APA/MLA Format Download EndNote Download BibTex|
Antigens, CD31 / metabolism
Chemokine CXCL12 / genetics, metabolism*
Culture Media, Conditioned / metabolism
Disease Models, Animal
Mesenchymal Stem Cell Transplantation*
Mesenchymal Stromal Cells / metabolism*
Myocardial Infarction / metabolism, pathology, physiopathology, surgery*
Myocytes, Cardiac / metabolism*, pathology
Receptors, CXCR4 / metabolism
Recovery of Function
Troponin T / metabolism
Vascular Endothelial Growth Factor A / genetics, metabolism*
Vascular Endothelial Growth Factor Receptor-1 / metabolism
Vascular Endothelial Growth Factor Receptor-3 / metabolism
Ventricular Function, Left
von Willebrand Factor / metabolism
|HL093429/HL/NHLBI NIH HHS; R01 HL093429/HL/NHLBI NIH HHS|
|0/Antigens, CD31; 0/Chemokine CXCL12; 0/Culture Media, Conditioned; 0/Cxcr4 protein, rat; 0/Receptors, CXCR4; 0/Troponin T; 0/VEGFA protein, human; 0/Vascular Endothelial Growth Factor A; 0/von Willebrand Factor; EC 18.104.22.168/Vascular Endothelial Growth Factor Receptor-1; EC 22.214.171.124/Vascular Endothelial Growth Factor Receptor-3|
|Cardiovasc Res. 2011 Aug 1;91(3):369-70
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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