Preventive cardioprotection of erythropoietin against doxorubicin-induced cardiomyopathy.

Preventive cardioprotection of erythropoietin against doxorubicin-induced cardiomyopathy. Research Abstract Details 

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Preventive cardioprotection of erythropoietin against doxorubicin-induced cardiomyopathy. Abstract Text:

Xing Chen,Yongli Chen,Yanyong Bi,Naikuan Fu,Chunyan Shan,Sili Wang,Shahid Aslam,Peixian Wang Wang,Jing Xu,Xing Chen,Yongli Chen,Yanyong Bi,Naikuan Fu,Chunyan Shan,Sili Wang,Shahid Aslam,Peixian Wang Wang,Jing Xu,

INTRODUCTION: Doxorubicin (DOX) is a highly effective chemotherapeutic agent related to dose-dependent cardiomyopathy. Recent evidence suggests that erythropoietin (EPO) can play a protective role in cardiovascular diseases by non-erythropoietic effects. In the present study, we tested the hypothesis that EPO may protect against DOX-induced cardiomyopathy through anti-apoptotic mechanisms both in vitro and in vivo. MATERIALS AND METHODS: Isolated neonatal Wistar rat cardiomyocytes were treated with vehicle, DOX with or without EPO, or EPO. Twenty-four hours later, the cells were used to determine cardiomyocyte apoptosis (TUNEL assay). Cardiomyopathy was induced in Wistar rats by intraperitoneal injections (IP) of DOX (2.5 mg/kg, six times for 2 weeks). EPO (2,500 U/kg, six times for 2 weeks) was administered simultaneously in the DOX+EPO group and the EPO group. Two weeks after the last administration, cardiac function was evaluated by echocardiography and invasive haemodynamic measurements. Rats were then sacrificed for histological and TUNEL analyses, with immunological detection for cardiac Troponin-T (cTnT), alpha-actinin, Bax and Bcl-2. RESULTS: EPO significantly ameliorated DOX-induced apoptosis of cultured cardiomyocytes as demonstrated by TUNEL assay. In the rat model, cardiac function significantly decreased in the DOX group. In contrast, the DOX+EPO group showed considerable improvement in cardiac function, inhibition of cardiomyocyte apoptosis, reduction of fibrosis, as well as up-regulation of Bcl-2 protein expression. CONCLUSIONS: Our results suggest that EPO exerts preventive cardioprotective effects on DOX-induced cardiomyopathy via anti-apoptotic pathways. The up-regulation of Bcl-2 protein expression may contribute to this.

Preventive cardioprotection of erythropoietin against doxorubicin-induced cardiomyopathy. Publishing Authors By Initials

X Chen,Y Chen,Y Bi,N Fu,C Shan,S Wang,S Aslam,PW Wang,J Xu,X Chen,Y Chen,Y Bi,N Fu,C Shan,S Wang,S Aslam,PW Wang,J Xu,

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Preventive cardioprotection of erythropoietin against doxorubicin-induced cardiomyopathy. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Cardiovascular drugs and therapy / sponsored by th

VOLUME: 21

Page Numbers: 367-74

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ISSN: 0920-3206

DAY: 26

MONTH: Oct

YEAR: 2007

Preventive cardioprotection of erythropoietin against doxorubicin-induced cardiomyopathy. Information

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LANGUAGE: eng

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Grant and Affiliation Information for Preventive cardioprotection of erythropoietin against doxorubicin-induced cardiomyopathy.

AFFILIATION: Department of Cardiology, General Hospital of Tianjin Medical University, Tianjin, China.

Country: United States

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MEDLINETA: Cardiovasc Drugs Ther

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