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Current Molecular Pharmacology

Volume 2 Issue 1
ISSN: 1874-4672
eISSN: 1874-4702

 

   All Titles

  Molecular Basis of Cardioprotection by Erythropoietin
  pp.56-69 (14) Authors: D. Burger, A. Xenocostas, Q. P. Feng
doi: 10.2174/1874467210902010056
   
      Abstract

Erythropoietin (EPO), a glycoprotein essential for red blood cell production acts on several non-erythropoietic tissues. The EPO receptor (EPOR) is expressed in a variety of cell types including neurons, endothelial cells, and cardiomyocytes. Recently, a number of reports have indicated that EPO preserves heart function in models of cardiac ischemia-reperfusion (I/R) injury. A diverse range of cellular/physiological processes is modulated by EPO and are thought to play a role in the preservation of heart function. In vivo, reductions in infarct size, apoptosis, oxidative stress, and inflammation have been reported. More recently, increases in angiogenesis and reductions in arrhythmias have been implicated in the cardioprotective effects of EPO. In vitro, EPO reduces apoptosis, oxidative stress, and inflammation. These cardioprotective effects appear to be mediated by a receptor interaction that is distinct from that responsible for EPO s erythropoietic effects. Downstream of receptor interactions, the activation of phosphatidylinositol-3 kinase (PI3-kinase) and Akt appear to mediate many of EPO's cardioprotective effects. However, there is emerging evidence for Akt-independent mechanisms of cardioprotection including the inhibition of glycogen synthase kinase 3β, as well as the activation of potassium channels, protein kinase C, and protein kinases such as ERK1/2. This review focuses on the effects of EPO in the heart and the molecular mechanisms by which EPO achieves its cardioprotective effects.

 
  Keywords: Erythropoietin, cardioprotection, myocardial infarction, ischemia and reperfusion, apoptosis, nitric oxide, signal transduction, angiogenesis
  Affiliation: Department of Physiology&Pharmacology, University of Western Ontario, London, Ontario, N6A 5C1 Canada.
 
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