Direct cardiac actions of erythropoietin (EPO): effects on cardiac contractility, BNP secretion and ischaemia/reperfusion injury.

Direct cardiac actions of erythropoietin (EPO): effects on cardiac contractility, BNP secretion and ischaemia/reperfusion injury. Research Abstract Details 

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Direct cardiac actions of erythropoietin (EPO): effects on cardiac contractility, BNP secretion and ischaemia/reperfusion injury. Abstract Text:

Jarkko Piuhola,Risto ,Jacqueline I Keenan,Mark B Hampton,A Mark Richards,Chris J Pemberton,Jarkko Piuhola,Risto Kerkelä,Jacqueline I Keenan,Mark B Hampton,A Mark Richards,Chris J Pemberton,

EPO (erythropoietin) has recently been shown to have protective actions upon the myocardium; however, the direct effects of EPO upon cardiac contractile and secretory functions are unknown and the signalling mechanisms are not well defined. In the present study, we provide the first evidence of direct cardiac contractile actions of EPO. In isolated perfused Sprague-Dawley rat hearts, a 30 min infusion of EPO significantly increased contractility in a dose-dependent fashion (maximal change 18+/-2% with 1 unit/ml EPO; P<0.005 compared with vehicle). Perfusate ET-1 (endothelin-1) increased transiently during EPO infusion, and the ET(A/)ET(B) antagonist bosentan abolished the inotropic response to EPO. BNP (B-type natriuretic peptide) secretion (28+/-8%; P<0.05) and nuclear transcription factor GATA-4 DNA-binding activity (51%; P<0.05) were both significantly increased by EPO and blocked by bosentan. In a model of global ischaemic injury, delivery of 1 unit/ml EPO during reperfusion significantly attenuated creatine kinase release (28+/-12%; P<0.05) and significantly improved contractile recovery (P<0.001), independent of ET(A) blockade. Apoptotic indices [assessed by TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling)/cleaved caspase-3-positive cells] were significantly decreased (P<0.01) by 1 unit/ml EPO during reperfusion alone, coincident with significantly increased phosphorylation of myocardial JAK2 (Janus kinase 2) and STAT3 (signal transducer and activator of transcription 3). Thus EPO directly enhances cardiac contractility and BNP secretion and alleviates ischemia/reperfusion injury via ET-1-dependent and -independent mechanisms respectively.

Direct cardiac actions of erythropoietin (EPO): effects on cardiac contractility, BNP secretion and ischaemia/reperfusion injury. Publishing Authors By Initials

J Piuhola,R ,JI Keenan,MB Hampton,AM Richards,CJ Pemberton,J Piuhola,R Kerkelä,JI Keenan,MB Hampton,AM Richards,CJ Pemberton,

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Direct cardiac actions of erythropoietin (EPO): effects on cardiac contractility, BNP secretion and ischaemia/reperfusion injury. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Clinical science (London, England : 1979)

VOLUME: 114

Page Numbers: 293-304

Journal Abbreviation: Clin. Sci.

ISSN: 1470-8736

DAY: 15

MONTH: Feb

YEAR: 2008

Direct cardiac actions of erythropoietin (EPO): effects on cardiac contractility, BNP secretion and ischaemia/reperfusion injury. Information

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LANGUAGE: eng

NlmUniqueID: 7905731

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AFFILIATION: Christchurch CardioEndocrine Research Group, University of Otago, Christchurch, New Zealand.

Country: England

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MEDLINETA: Clin Sci (Lond)

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