Mechanism of the cardioprotection of rhEPO pretreatment on suppressing the inflammatory response in ischemia–reperfusion

Erythropoietin (EPO), originally known for its role in stimulation of erythropoiesis, has recently been shown to have a dramatic protective effect in animal models of myocardial ischemia–reperfusion (I–R) injury. However, the precise mechanisms remain unclear. We tried to study the anti-inflammatory...

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Bibliographic Details
Published in:	Life sciences (1973) Vol. 78; no. 19; pp. 2255 - 2264
Main Authors:	Liu, Xiaoming, Xie, Weiying, Liu, Pichu, Duan, Manlin, Jia, Zhen, Li, Wei, Xu, Jianguo
Format:	Journal Article
Language:	English
Published:	Netherlands Elsevier Inc 04-04-2006
Subjects:	Animals Anti-Inflammatory Agents, Non-Steroidal - therapeutic use AP-1 Cardiotonic Agents - therapeutic use Disease Models, Animal Electrophoretic Mobility Shift Assay Enzyme-Linked Immunosorbent Assay Erythropoietin Erythropoietin - therapeutic use Humans IL-10 Ischemia–reperfusion Male Mitochondria, Heart - drug effects Mitochondria, Heart - enzymology Mitochondria, Heart - ultrastructure Myocardial Infarction - etiology Myocardial Infarction - pathology Myocardial Infarction - prevention & control Myocardial Reperfusion Injury - complications Myocardial Reperfusion Injury - drug therapy Myocardial Reperfusion Injury - pathology Myocardium - enzymology Myocardium - ultrastructure Neutrophil Infiltration - drug effects NF-κB Nuclear Proteins - metabolism Peroxidase - metabolism Rats Rats, Sprague-Dawley Recombinant Proteins Reverse Transcriptase Polymerase Chain Reaction NF-κB Ischemia–reperfusion Erythropoietin AP-1 IL-10
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Summary:	Erythropoietin (EPO), originally known for its role in stimulation of erythropoiesis, has recently been shown to have a dramatic protective effect in animal models of myocardial ischemia–reperfusion (I–R) injury. However, the precise mechanisms remain unclear. We tried to study the anti-inflammatory properties of recombinant human erythropoietin (rhEPO) using an in vivo myocardial I–R rat model, which was established by 30 min ligation of left descending coronary and 3 h reperfusion. rhEPO or saline solution was intraperitoneally injected 24 h before I–R insult. The infarct size was measured by triphenyltetrazolium chloride (TTC)–Evans blue technique. Myeloperoxidase (MPO) activity and tissue neutrophil infiltration were studied. Ultrastructural organizations were observed and semiquantitatively evaluated. Tumor necrosis-alpha (TNF-α), interleukin-6 (IL-6), and IL-10 concentrations of left ventricle were analyzed by enzyme-linked immunosorbance assays; intercellular adhesion molecule-1 (ICAM-1) by reverse-transcription polymerase chain reaction; and nuclear factor-kappa B (NF-κB) and activator protein 1 (AP-1) by electrophoretic mobility shift assay, respectively. We found that a single bolus injection of 5000 units/kg of rhEPO 24 h before insult remarkably reduced infarct size and neutrophil infiltration. It greatly attenuated I–R-induced NF-κB and AP-1 activation with decreased TNF-α, IL-6, and ICAM-1 production, but enhanced IL-10 production. In conclusion, the cardioprotection of EPO may be due in part to the suppression of the inflammatory response via down-regulation of NF-κB and AP-1 induced by I–R. IL-10 was also suggested to play a protective role through another independent mechanism involved in cardioprotection of rhEPO.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0024-3205 1879-0631
DOI:	10.1016/j.lfs.2005.09.053