Erythropoietin, modified to not stimulate red blood cell production, retains its cardioprotective properties
- Authors
- Moon, Chanil; Krawczyk, Melissa; Paik, Doojin; Coleman, Thomas; Brines, Michael; Juhaszova, Magdalena; Sollott, Steven J.; Lakatta, Edward G; Talan, Mark I
- Issue Date
- Mar-2006
- Publisher
- AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
- Citation
- JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, v.316, no.3, pp.999 - 1005
- Indexed
- SCIE
SCOPUS
- Journal Title
- JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
- Volume
- 316
- Number
- 3
- Start Page
- 999
- End Page
- 1005
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/181684
- DOI
- 10.1124/jpet.105.094854
- ISSN
- 0022-3565
- 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 mu g/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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