Cardiomyocyte Atrophy, an Underestimated Contributor in Doxorubicin-Induced Cardiotoxicity

De-Shu Chen; Jing Yan; Ping-Zhen Yang

doi:10.3389/fcvm.2022.812578

Cardiomyocyte Atrophy, an Underestimated Contributor in Doxorubicin-Induced Cardiotoxicity

Front Cardiovasc Med. 2022 Feb 25:9:812578. doi: 10.3389/fcvm.2022.812578. eCollection 2022.

Authors

De-Shu Chen^{1

2

3}, Jing Yan^{1

2

3}, Ping-Zhen Yang^{1

2

3}

Affiliations

¹ Department of Cardiology, Laboratory of Heart Center, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
² Heart Center of Zhujiang Hospital, Guangdong Provincial Biomedical Engineering Technology Research Center for Cardiovascular Disease, Guangzhou, China.
³ Heart Center of Zhujiang Hospital, Sino-Japanese Cooperation Platform for Translational Research in Heart Failure, Guangzhou, China.

Abstract

Left ventricular (LV) mass loss is prevalent in doxorubicin (DOX)-induced cardiotoxicity and is responsible for the progressive decline of cardiac function. Comparing with the well-studied role of cell death, the part of cardiomyocyte atrophy (CMA) playing in the LV mass loss is underestimated and the knowledge of the underlying mechanism is still limited. In this review, we summarized the recent advances in the DOX-induced CMA. We found that the CMA caused by DOX is associated with the upregulation of FOXOs and "atrogenes," the activation of transient receptor potential canonical 3-NADPH oxidase 2 (TRPC3-Nox2) axis, and the suppression of IGF-1-PI3K signaling pathway. The imbalance of anabolic and catabolic process may be the common final pathway of these mechanisms. At last, we provided some strategies that have been demonstrated to alleviate the DOX-induced CMA in animal models.

Keywords: cardiomyocyte atrophy; cardiotoxicity; cell death; doxorubicin; left ventricular mass loss.

Publication types

Review