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Preventive Cardioprotection of Erythropoietin Against Doxorubicin-induced Cardiomyopathy

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Abstract

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), α-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.

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Authors and Affiliations

  1. Department of Cardiology, General Hospital of Tianjin Medical University, Tianjin, China

    Xing Chen, Yanyong Bi, Shahid Aslam & Peixian Wang

  2. Tianjin Chest Hospital, Tianjin, China

    Yongli Chen, Naikuan Fu & Jing Xu

  3. Metabolic Diseases Hospital, Tianjin Medical University, Tianjin, China

    Chunyan Shan

  4. State Key Laboratory of Experimental Hematology, Institute of Hematology, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China

    Sili Wang

  5. Department of Cardiology, Tianjin Chest Hospital, Tianjin, 300051, China

    Jing Xu

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  1. Xing Chen
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Correspondence to Jing Xu.

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Chen, X., Chen, Y., Bi, Y. et al. Preventive Cardioprotection of Erythropoietin Against Doxorubicin-induced Cardiomyopathy. Cardiovasc Drugs Ther 21, 367–374 (2007). https://doi.org/10.1007/s10557-007-6052-0

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