Phosphatidylinositol-3-Kinase Signaling Is Required for Erythropoietin-Mediated Acute Protection against Myocardial Ischemia/ Reperfusion Injury

Zheqing Cai; Gregg L. Semenza

doi:10.1161/01.CIR.0000127954.98131.23

Phosphatidylinositol-3-Kinase Signaling Is Required for Erythropoietin-Mediated Acute Protection against Myocardial Ischemia/ Reperfusion Injury

Zheqing Cai, Gregg L. Semenza

School of Medicine

Research output: Contribution to journal › Article › peer-review

176 Scopus citations

Abstract

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 wormannin 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.

Original language	English (US)
Pages (from-to)	2050-2053
Number of pages	4
Journal	Circulation
Volume	109
Issue number	17
DOIs	https://doi.org/10.1161/01.CIR.0000127954.98131.23
State	Published - May 4 2004

Keywords

Erythropoietin
Ischemia
Myocardial infarction
Reperfusion

ASJC Scopus subject areas

Cardiology and Cardiovascular Medicine
Physiology (medical)

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10.1161/01.CIR.0000127954.98131.23

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title = "Phosphatidylinositol-3-Kinase Signaling Is Required for Erythropoietin-Mediated Acute Protection against Myocardial Ischemia/ Reperfusion Injury",

abstract = "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 wormannin 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.",

keywords = "Erythropoietin, Ischemia, Myocardial infarction, Reperfusion",

author = "Zheqing Cai and Semenza, {Gregg L.}",

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T1 - Phosphatidylinositol-3-Kinase Signaling Is Required for Erythropoietin-Mediated Acute Protection against Myocardial Ischemia/ Reperfusion Injury

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AU - Semenza, Gregg L.

PY - 2004/5/4

Y1 - 2004/5/4

N2 - 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 wormannin 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.

AB - 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 wormannin 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.

KW - Erythropoietin

KW - Ischemia

KW - Myocardial infarction

KW - Reperfusion

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Phosphatidylinositol-3-Kinase Signaling Is Required for Erythropoietin-Mediated Acute Protection against Myocardial Ischemia/ Reperfusion Injury

Abstract

Keywords

ASJC Scopus subject areas

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