A novel protective effect of erythropoietin in the infarcted heart.
Erythropoietin (EPO) has been shown to protect neurons from ischemic stroke, but can also increase thrombotic events and mortality rates in patients with ischemic heart disease. We reasoned that benefits of EPO might be offset by increases in hematocrit and evaluated the direct effects of EPO in the ischemic heart. We show that preconditioning with EPO protects H9c2 myoblasts in vitro and cardiomyocytes in vivo against ischemic injury. EPO treatment leads to significantly improved cardiac function following myocardial infarction. This protection is associated with mitigation of myocyte apoptosis, translating into more viable myocardium and less ventricular dysfunction. EPO-mediated myocyte survival appears to involve Akt activation. Importantly, cardioprotective effects of EPO were seen without an increase in hematocrit (eliminating oxygen delivery as an etiologic factor in myocyte survival and function), demonstrating that EPO can directly protect the ischemic and infarcted heart.
Parsa
Cyrus J
CJ
Department of Surgery, Duke University Medical Center, Durham, North Carolina, USA.
Matsumoto
Akio
A
Kim
Jihee
J
Riel
Ryan U
RU
Pascal
Laura S
LS
Walton
G Brant
GB
Thompson
Richard B
RB
Petrofski
Jason A
JA
Annex
Brian H
BH
Stamler
Jonathan S
JS
Koch
Walter J
WJ
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D004921:Erythropoietin / Q000627:therapeutic use*; D020287:In Situ Nick-End Labeling; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000503:physiopathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D020011:Protective Agents / Q000627:therapeutic use*; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D051381:Rats
D004921:Erythropoietin; D020928:Mitogen-Activated Protein Kinases; D019869:Phosphatidylinositol 3-Kinases; D020011:Protective Agents; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; C494920:Akt1 protein, rat