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Research ArticleCARDIOVASCULAR

Erythropoietin, Modified to Not Stimulate Red Blood Cell Production, Retains Its Cardioprotective Properties

Chanil Moon, Melissa Krawczyk, Doojin Paik, Thomas Coleman, Michael Brines, Magdalena Juhaszova, Steven J. Sollott, Edward G. Lakatta and Mark I. Talan
Journal of Pharmacology and Experimental Therapeutics March 2006, 316 (3) 999-1005; DOI: https://doi.org/10.1124/jpet.105.094854
Chanil Moon
Laboratory of Cardiovascular Sciences, Gerontology Research Center, National Institute on Aging, Baltimore, Maryland (C.M., M.K., M.J., S.J.S., E.G.L., M.I.T.); Department of Anatomy and Cell Biology, Hanyang University, Seoul, Korea (D.P.); and Kenneth S. Warren Institute and Warren Pharmaceuticals, Ossining, New York (T.C., M.B.)
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Melissa Krawczyk
Laboratory of Cardiovascular Sciences, Gerontology Research Center, National Institute on Aging, Baltimore, Maryland (C.M., M.K., M.J., S.J.S., E.G.L., M.I.T.); Department of Anatomy and Cell Biology, Hanyang University, Seoul, Korea (D.P.); and Kenneth S. Warren Institute and Warren Pharmaceuticals, Ossining, New York (T.C., M.B.)
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Doojin Paik
Laboratory of Cardiovascular Sciences, Gerontology Research Center, National Institute on Aging, Baltimore, Maryland (C.M., M.K., M.J., S.J.S., E.G.L., M.I.T.); Department of Anatomy and Cell Biology, Hanyang University, Seoul, Korea (D.P.); and Kenneth S. Warren Institute and Warren Pharmaceuticals, Ossining, New York (T.C., M.B.)
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Thomas Coleman
Laboratory of Cardiovascular Sciences, Gerontology Research Center, National Institute on Aging, Baltimore, Maryland (C.M., M.K., M.J., S.J.S., E.G.L., M.I.T.); Department of Anatomy and Cell Biology, Hanyang University, Seoul, Korea (D.P.); and Kenneth S. Warren Institute and Warren Pharmaceuticals, Ossining, New York (T.C., M.B.)
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Michael Brines
Laboratory of Cardiovascular Sciences, Gerontology Research Center, National Institute on Aging, Baltimore, Maryland (C.M., M.K., M.J., S.J.S., E.G.L., M.I.T.); Department of Anatomy and Cell Biology, Hanyang University, Seoul, Korea (D.P.); and Kenneth S. Warren Institute and Warren Pharmaceuticals, Ossining, New York (T.C., M.B.)
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Magdalena Juhaszova
Laboratory of Cardiovascular Sciences, Gerontology Research Center, National Institute on Aging, Baltimore, Maryland (C.M., M.K., M.J., S.J.S., E.G.L., M.I.T.); Department of Anatomy and Cell Biology, Hanyang University, Seoul, Korea (D.P.); and Kenneth S. Warren Institute and Warren Pharmaceuticals, Ossining, New York (T.C., M.B.)
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Steven J. Sollott
Laboratory of Cardiovascular Sciences, Gerontology Research Center, National Institute on Aging, Baltimore, Maryland (C.M., M.K., M.J., S.J.S., E.G.L., M.I.T.); Department of Anatomy and Cell Biology, Hanyang University, Seoul, Korea (D.P.); and Kenneth S. Warren Institute and Warren Pharmaceuticals, Ossining, New York (T.C., M.B.)
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Edward G. Lakatta
Laboratory of Cardiovascular Sciences, Gerontology Research Center, National Institute on Aging, Baltimore, Maryland (C.M., M.K., M.J., S.J.S., E.G.L., M.I.T.); Department of Anatomy and Cell Biology, Hanyang University, Seoul, Korea (D.P.); and Kenneth S. Warren Institute and Warren Pharmaceuticals, Ossining, New York (T.C., M.B.)
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Mark I. Talan
Laboratory of Cardiovascular Sciences, Gerontology Research Center, National Institute on Aging, Baltimore, Maryland (C.M., M.K., M.J., S.J.S., E.G.L., M.I.T.); Department of Anatomy and Cell Biology, Hanyang University, Seoul, Korea (D.P.); and Kenneth S. Warren Institute and Warren Pharmaceuticals, Ossining, New York (T.C., M.B.)
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Abstract

Erythropoietin (EPO), a hematopoietic cytokine, possesses strong antiapoptotic, tissue-protective properties. For clinical applications, it is desirable to separate the hematopoietic and tissue-protective properties. Recently introduced carbamylated erythropoietin (CEPO) does not stimulate the erythropoiesis but retains the antiapoptotic and neuroprotective effects. We tested the ability of CEPO to protect cardiac tissue from toxin-induced and oxidative stress in vitro and ischemic damage in vivo and compared these effects with the effects of EPO. CEPO reduced by 50% the extent of staurosporine-induced apoptosis in isolated rats' cardiomyocytes and increased by 25% the reactive oxygen species threshold for induction of the mitochondrial permeability transition. In an experimental model of myocardial infarction induced by permanent ligation of a coronary artery in rats, similarly to EPO, a single bolus injection of 30 μg/kg b.wt. of CEPO immediately after coronary ligation reduced apoptosis in the myocardial area at risk, examined 24 h later, by 50%. Left ventricular remodeling (ventricular dilation) and functional decline (fall in ejection fraction) assessed by repeated echocardiography were significantly and similarly attenuated in CEPO- and EPO-treated rats. Four weeks after coronary ligation, the myocardial infarction (MI) size in CEPO- and EPO-treated rats was half of that in untreated coronary-ligated animals. Unlike EPO, CEPO had no effect on hematocrit. The antiapoptotic cardioprotective effects of CEPO, shown by its ability to limit both post-MI left ventricular remodeling and the extent of the myocardial scar in the model of permanent coronary artery ligation in rats, demonstrate comparable potency to that of native (nonmodified) EPO.

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Journal of Pharmacology and Experimental Therapeutics: 316 (3)
Journal of Pharmacology and Experimental Therapeutics
Vol. 316, Issue 3
1 Mar 2006
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Research ArticleCARDIOVASCULAR

Erythropoietin, Modified to Not Stimulate Red Blood Cell Production, Retains Its Cardioprotective Properties

Chanil Moon, Melissa Krawczyk, Doojin Paik, Thomas Coleman, Michael Brines, Magdalena Juhaszova, Steven J. Sollott, Edward G. Lakatta and Mark I. Talan
Journal of Pharmacology and Experimental Therapeutics March 1, 2006, 316 (3) 999-1005; DOI: https://doi.org/10.1124/jpet.105.094854

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Research ArticleCARDIOVASCULAR

Erythropoietin, Modified to Not Stimulate Red Blood Cell Production, Retains Its Cardioprotective Properties

Chanil Moon, Melissa Krawczyk, Doojin Paik, Thomas Coleman, Michael Brines, Magdalena Juhaszova, Steven J. Sollott, Edward G. Lakatta and Mark I. Talan
Journal of Pharmacology and Experimental Therapeutics March 1, 2006, 316 (3) 999-1005; DOI: https://doi.org/10.1124/jpet.105.094854
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