Phosphatidylinositol-3-kinase signaling is required for erythropoietin-mediated acute protection against myocardial ischemia/reperfusion injury

被引：179
作者：
Cai, ZQ
Semenza, GL
机构：
[1] Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA
[2] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Inst Cell Engn, Baltimore, MD 21205 USA
来源：
CIRCULATION | 2004年 / 109卷 / 17期
关键词：
erythropoietin; ischemia; reperfusion; myocardial infarction;
D O I：
10.1161/01.CIR.0000127954.98131.23
中图分类号：
R5 [内科学];
学科分类号：
1002 ; 100201 ;
摘要：
Background - Parenteral administration of recombinant human erythropoietin (rhEPO) to rats induces protection against myocardial ischemia/reperfusion injury 24 hours later. However, the mechanisms by which rhEPO mediates protection have not been determined. Methods and Results - rhEPO was perfused into isolated rat hearts over 15 minutes immediately before 30 minutes of no-flow ischemia and 45 minutes of reperfusion. Compared with saline-perfused control hearts, recovery of left ventricular developed pressure was increased in rhEPO-perfused hearts. rhEPO also increased AKT activity and decreased apoptosis. All of these effects were blocked when the phosphatidylinositol-3-kinase inhibitor wortmannin was infused with rhEPO. Conclusions - rhEPO provides immediate protection against ischemia/reperfusion injury in the isolated perfused rat heart that is mediated by the phosphatidylinositol-3-kinase pathway.
引用
收藏
页码：2050 / 2053
页数：4
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