Open AccessIntracardiac injection of erythropoietin induces stem cell recruitment and improves cardiac functions in a rat myocardial infarction model
Author(s) -
Klopsch Christian,
Furlani Dario,
Gäbel Ralf,
Li Wenzhong,
Pittermann Erik,
Ugurlucan Murat,
Kundt Guenther,
Zingler Christiana,
Titze Ulf,
Wang Weiwei,
Ong LeeLee,
Wagner Klaus,
Li RenKe,
Ma Nan,
Steinhoff Gustav
Publication year - 2009
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2008.00546.x
Subject(s) - erythropoietin , intracardiac injection , medicine , myocardial infarction , cardiology , ventricular remodeling , cardiac function curve , infarction , endocrinology , heart failure
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 mm; 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.