Chen De-Shu, Yan Jing, Yang Ping-Zhen
Department of Cardiology, Laboratory of Heart Center, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
Heart Center of Zhujiang Hospital, Guangdong Provincial Biomedical Engineering Technology Research Center for Cardiovascular Disease, Guangzhou, China.
Front Cardiovasc Med. 2022 Feb 25;9:812578. doi: 10.3389/fcvm.2022.812578. eCollection 2022.
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.
左心室（LV）质量损失在阿霉素（DOX）诱导的心脏毒性中很常见，并且是心脏功能逐渐衰退的原因。与细胞死亡这一已得到充分研究的作用相比，心肌细胞萎缩（CMA）在左心室质量损失中所起的作用被低估，且对其潜在机制的了解仍然有限。在本综述中，我们总结了DOX诱导CMA的最新进展。我们发现，DOX引起的CMA与FOXO和“萎缩基因”的上调、瞬时受体电位阳离子通道亚家族C成员3-烟酰胺腺嘌呤二核苷酸磷酸氧化酶2（TRPC3-Nox2）轴的激活以及胰岛素样生长因子1-磷脂酰肌醇3-激酶（IGF-1-PI3K）信号通路的抑制有关。合成代谢和分解代谢过程的失衡可能是这些机制的共同最终途径。最后，我们提供了一些已被证明可在动物模型中减轻DOX诱导的CMA的策略。
