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Updated: Nov 18, 2025

A Doxorubicin-Induced Murine Model of Dilated Cardiomyopathy In Vivo
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A Doxorubicin-Induced Murine Model of Dilated Cardiomyopathy In Vivo

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Klotho attenuated Doxorubicin-induced cardiomyopathy by alleviating Dynamin-related protein 1 - mediated

Xiaodong Zhuang1, Xiuting Sun1, Huimin Zhou1

  • 1Department of Cardiology, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China; Key Laboratory on Assisted Circulation, Ministry of Health, Guangzhou, China.

Mechanisms of Ageing and Development
|February 4, 2021
PubMed

Insights

Klotho protects against Doxorubicin-induced cardiotoxicity by reducing apoptosis and mitochondrial fission. This involves down-regulating Dynamin-related protein 1 (Drp1) expression, offering new therapeutic targets for heart damage.

Area of Science:

  • Cardiology
  • Molecular Biology
  • Biochemistry

Background:

  • Doxorubicin (Dox) is a potent chemotherapy agent with dose-limiting cardiotoxicity, potentially leading to dilated cardiomyopathy and heart failure.
  • Previous research indicated Klotho's protective role in hyperglycemia-induced cardiomyopathy.
  • The potential of Klotho in mitigating Dox-induced cardiotoxicity remained unexplored.

Purpose of the Study:

  • To investigate the protective effects of Klotho against Doxorubicin-induced cardiotoxicity.
  • To elucidate the underlying mechanisms, focusing on apoptosis, mitochondrial dysfunction, and Dynamin-related protein 1 (Drp1) expression.

Main Methods:

  • In vitro studies using neonatal rat ventricular cardiomyocytes and H9c2 cells treated with Dox and Klotho.
  • In vivo studies utilizing a Dox-induced cardiotoxicity mouse model (C57BL/6).
  • Assessment of cardiac function, serum enzyme activity, apoptosis, mitochondrial dysfunction, and Drp1 expression (including phosphorylation at Ser 616).

Main Results:

  • Klotho pretreatment significantly reduced Dox-induced apoptosis in cardiomyocytes and suppressed cardiac cell death in mice.
  • Klotho administration improved cardiac function in Dox-treated mice.
  • Dox treatment increased Dynamin-related protein 1 (Drp1) expression and Ser 616 phosphorylation, which was attenuated by Klotho. Overexpression of Drp1 exacerbated Dox-induced heart injury, and Klotho mitigated this effect.

Conclusions:

  • Klotho alleviates Doxorubicin-induced cardiotoxicity by reducing apoptosis and mitochondrial fission.
  • The protective mechanism involves the down-regulation of Dynamin-related protein 1 (Drp1) expression.
  • Klotho presents a promising therapeutic target for preventing or treating Doxorubicin-induced cardiomyopathy.

Keywords:
CardiotoxicityDoxorubicinDrp1KlothoMitochondrial fission

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