Molecular Mechanisms of Cardiomyocyte Death in Drug-Induced Cardiotoxicity

Wanjun Ma; Shanshan Wei; Bikui Zhang; Wenqun Li

doi:10.3389/fcell.2020.00434

Molecular Mechanisms of Cardiomyocyte Death in Drug-Induced Cardiotoxicity

Front Cell Dev Biol. 2020 Jun 3:8:434. doi: 10.3389/fcell.2020.00434. eCollection 2020.

Authors

Wanjun Ma^{1

2}, Shanshan Wei^{1

2}, Bikui Zhang^{1

2}, Wenqun Li^{1

2}

Affiliations

¹ Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, China.
² Institute of Clinical Pharmacy, Central South University, Changsha, China.

Abstract

Homeostatic regulation of cardiomyocytes plays a crucial role in maintaining the normal physiological activity of cardiac tissue. Severe cardiotoxicity results in cardiac diseases including but not limited to arrhythmia, myocardial infarction and myocardial hypertrophy. Drug-induced cardiotoxicity limits or forbids further use of the implicated drugs. Such drugs that are currently available in the clinic include anti-tumor drugs (doxorubicin, cisplatin, trastuzumab, etc.), antidiabetic drugs (rosiglitazone and pioglitazone), and an antiviral drug (zidovudine). This review focused on cardiomyocyte death forms and related mechanisms underlying clinical drug-induced cardiotoxicity, including apoptosis, autophagy, necrosis, necroptosis, pryoptosis, and ferroptosis. The key proteins involved in cardiomyocyte death signaling were discussed and evaluated, aiming to provide a theoretical basis and target for the prevention and treatment of drug-induced cardiotoxicity in the clinical practice.

Keywords: apoptosis; autophagy; cardiomyocytes; cardiotoxicity; cell death; necrosis.

Publication types

Review