Erythropoietin prevents the acute myocardial inflammatory response induced by ischemia/reperfusion via induction of AP-1

Tao Rui; Qingping Feng; Ming Lei; Jianhua Zhang; Tianqing Peng; Ming Xu; E Dale Abel; Anargyros Xenocostas; Peter R Kvietys

doi:10.1016/j.cardiores.2004.11.019

Back

Erythropoietin prevents the acute myocardial inflammatory response induced by ischemia/reperfusion via induction of AP-1

Journal article

Peer reviewed

Erythropoietin prevents the acute myocardial inflammatory response induced by ischemia/reperfusion via induction of AP-1

Tao Rui, Qingping Feng, Ming Lei, Jianhua Zhang, Tianqing Peng, Ming Xu, E Dale Abel, Anargyros Xenocostas and Peter R Kvietys

Cardiovascular research, Vol.65(3), pp.719-727

02/15/2005

DOI: 10.1016/j.cardiores.2004.11.019

PMID: 15664399

View Online

Abstract

Erythropoietin (EPO) prevents the myocardial dysfunction induced by ischemia/reperfusion (I/R). Since I/R-induced myocardial dysfunction is associated with an acute inflammatory response, we assessed the anti-inflammatory properties of EPO using in vitro and in vivo models of I/R. Isolated cardiac myocytes were exposed to anoxia/reoxygenation (A/R; the in vitro counterpart to I/R). Hearts were challenged with I/R in situ. In vitro, A/R increased myocyte oxidant stress and converted the myocytes to a proinflammatory phenotype (these myocytes induced PMN transendothelial migration). Pretreatment of the myocytes with EPO prevented the A/R-induced proinflammatory effects. EPO increased myocyte (1) nuclear translocation of AP-1 (c-fos/c-jun), (2) eNOS, but not iNOS, protein expression, and (3) NO production. An AP-1 "decoy" oligonucleotide prevented the induction of eNOS by EPO and reversed the beneficial effect of EPO. An inhibitor of phosphatidylinostol 3 (PI3)-kinase prevented the nuclear translocation of AP-1 induced by EPO. In vivo, in wild type mice, I/R induced an increase in myocardial MPO activity (indicative of PMN infiltration); an effect prevented by pretreatment of the mice with EPO. This anti-inflammatory effect of EPO was not observed in cardiac specific c-fos(-/-) mice. Collectively, these findings indicate that EPO can ameliorate the myocardial inflammatory response in both in vitro and in vivo models of I/R. This beneficial effect of EPO is mediated by eNOS-derived NO via a PI3-kinase-dependent activation of AP-1.

Oxidative Stress

Erythropoietin - therapeutic use

Mice, Inbred C57BL

Cells, Cultured

Nitric Oxide Synthase Type III

Nitric Oxide - physiology

Nitric Oxide Synthase Type II

Myocardial Reperfusion Injury - metabolism

Animals

Myocytes, Cardiac - drug effects

Anti-Inflammatory Agents, Non-Steroidal - therapeutic use

Transcription Factor AP-1 - physiology

Myocytes, Cardiac - metabolism

Mice

Nitric Oxide Synthase - metabolism

Myocardial Reperfusion Injury - prevention & control

Details

Title: Subtitle: Erythropoietin prevents the acute myocardial inflammatory response induced by ischemia/reperfusion via induction of AP-1
Creators: Tao Rui - Vascular Cell Biology Laboratory, Lawson Health Research Institute, University of Western Ontario, London, ON, Canada N6A 4G5
Qingping Feng
Ming Lei
Jianhua Zhang
Tianqing Peng
Ming Xu
E Dale Abel
Anargyros Xenocostas
Peter R Kvietys
Resource Type: Journal article
Publication Details: Cardiovascular research, Vol.65(3), pp.719-727
Publisher: England
DOI: 10.1016/j.cardiores.2004.11.019
PMID: 15664399
ISSN: 0008-6363
eISSN: 1755-3245
Language: English
Date published: 02/15/2005
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology; Endocrinology and Metabolism; Internal Medicine
Record Identifier: 9984025285902771

Metrics

14 Record Views

123 Times Cited - Web of Science

See more details