Asialoerythropoietin, a nonerythropoietic derivative of erythropoietin, displays broad anti-heart failure activity

Circulation. Heart Failure
Toshiaki TakeyamaShinya Minatoguchi

Abstract

We investigated the effects of asialoerythropoietin (asialoEPO), a nonerythrogenic erythropoietin derivative, on 3 murine models of heart failure with different etiologies. Doxorubicin (15 mg/kg) induced heart failure within 2 weeks (toxic cardiomyopathy). Treatment with asialoEPO (6.9 μg/kg) for 2 weeks thereafter attenuated the associated left ventricular dysfunction and dilatation. In addition, the asialoEPO-treated heart showed less myocardial fibrosis, inflammation, and oxidative damage, and diminished atrophic cardiomyocyte degeneration, which was accompanied by restored expression of GATA-4 and sarcomeric proteins. Mice with large 6-week-old myocardial infarctions exhibited marked left ventricular dysfunction with adverse remodeling (ischemic cardiomyopathy). AsialoEPO treatment for 4 weeks significantly mitigated progression of the dysfunction and remodeling and reduced myocardial fibrosis, inflammation, and oxidative damage. Finally, 25-week-old δ-sarcoglycan-deficient mice (genetic cardiomyopathy) were treated with asialoEPO for 5 weeks. AsialoEPO mitigated the progressive cardiac remodeling and dysfunction through cardiomyocyte hypertrophy, and upregulated expression of GATA-4 and sarcomeric proteins. AsialoEPO appea...Continue Reading

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Citations

Jan 15, 2013·Cardiovascular Drugs and Therapy·Takao YanagawaYoshifusa Aizawa
Oct 31, 2012·International Journal of Molecular Sciences·Kenneth MaieseShaohui Wang
May 16, 2015·The American Journal of Pathology·Kentaro MorishitaShinya Minatoguchi
Jan 1, 2014·International Journal of Cardiology·Fabian Sanchis-GomarGiuseppe Lippi
Oct 21, 2016·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Krisztina KissPéter Bencsik
May 20, 2016·PloS One·Chiharu YokoyamaShinya Minatoguchi
Feb 11, 2016·Biochemistry Insights·Jianmin ChenXiao Zhang
Apr 9, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Liasmine HaineNicolas Voituron

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