Document Detail

Intracardiac injection of erythropoietin induces stem cell recruitment and improves cardiac functions in a rat myocardial infarction model.
MedLine Citation:
PMID:  19449462     Owner:  NLM     Status:  MEDLINE    
Erythropoietin (EPO) protects the myocardium from ischaemic injury and promotes beneficial remodelling. We assessed the therapeutic efficacy of intracardiac EPO injection and EPO-mediated stem cell homing in a rat myocardial infarction (MI) model. Following MI, EPO (3000 U/kg) or saline was delivered by intracardiac injection. Compared to myocardial infarction control group (MIC), EPO significantly improved left ventricular function (n =11-14, P < 0.05) and decreased right ventricular wall stress (n = 8, P < 0.05) assessed by pressure-volume loops after 6 weeks. MI-EPO hearts exhibited smaller infarction size (20.1 +/- 1.1% versus 27.8 +/- 1.2%; n = 6-8, P < 0.001) and greater capillary density (338.5 +/- 14.7 versus 259.8 +/- 9.2 vessels per mm2; n = 6-8, P < 0.001) than MIC hearts. Direct EPO injection reduced post-MI myocardial apoptosis by approximately 41% (0.27 +/- 0.03% versus 0.42 +/- 0.03%; n = 6, P= 0.005). The chemoattractant SDF-1 was up-regulated significantly assessed by quantitative realtime PCR and immunohistology. c-Kit(+) and CD34(+) stem cells were significantly more numerous in MI-EPO than in MIC at 24 hrs in peripheral blood (n = 7, P < 0.05) and 48 hrs in the infarcted hearts (n = 6, P < 0.001). Further, the mRNAs of Akt, eNOS and EPO receptor were significantly enhanced in MI-EPO hearts (n = 7, P < 0.05). Intracardiac EPO injection restores myocardial functions following MI, which may attribute to the improved early recruitment of c-Kit(+) and CD34(+) stem cells via the enhanced expression of chemoattractant SDF-1.
Christian Klopsch; Dario Furlani; Ralf Gäbel; Wenzhong Li; Erik Pittermann; Murat Ugurlucan; Guenther Kundt; Christiana Zingler; Ulf Titze; Weiwei Wang; Lee-Lee Ong; Klaus Wagner; Ren-Ke Li; Nan Ma; Gustav Steinhoff
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cellular and molecular medicine     Volume:  13     ISSN:  1582-4934     ISO Abbreviation:  J. Cell. Mol. Med.     Publication Date:  2009 Apr 
Date Detail:
Created Date:  2009-05-15     Completed Date:  2009-07-08     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101083777     Medline TA:  J Cell Mol Med     Country:  England    
Other Details:
Languages:  eng     Pagination:  664-79     Citation Subset:  IM    
Department of Cardiac Surgery, University of Rostock, Germany.
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MeSH Terms
Apoptosis / drug effects
Cell Survival / drug effects
Chemokine CXCL12 / metabolism
Disease Models, Animal
Erythropoietin, Recombinant / administration & dosage*,  pharmacology,  therapeutic use*
Heart Function Tests*
Hematopoietic Stem Cell Mobilization*
Matrix Metalloproteinase 2 / metabolism
Myocardial Infarction / drug therapy*,  enzymology,  pathology,  physiopathology*
Myocytes, Cardiac / cytology,  drug effects
Neovascularization, Physiologic / drug effects
Receptors, CXCR4 / metabolism
Receptors, Erythropoietin / metabolism
Troponin T / metabolism
Up-Regulation / drug effects
Reg. No./Substance:
0/Chemokine CXCL12; 0/Cxcr4 protein, rat; 0/Erythropoietin, Recombinant; 0/Receptors, CXCR4; 0/Receptors, Erythropoietin; 0/Troponin T; EC Metalloproteinase 2

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