Zhou Liuhua, Sun Jiateng, Gu Lingfeng, Wang Sibo, Yang Tongtong, Wei Tianwen, Shan Tiankai, Wang Hao, Wang Liansheng
Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Front Cell Dev Biol. 2021 Nov 26;9:794879. doi: 10.3389/fcell.2021.794879. eCollection 2021.
Abnormalities in programmed cell death (PCD) signaling cascades can be observed in the development and progression of various cardiovascular diseases, such as apoptosis, necrosis, pyroptosis, ferroptosis, and cell death associated with autophagy. Aberrant activation of PCD pathways is a common feature leading to excessive cardiac remodeling and heart failure, involved in the pathogenesis of various cardiovascular diseases. Conversely, timely activation of PCD remodels cardiac structure and function after injury in a spatially or temporally restricted manner and corrects cardiac development similarly. As many cardiovascular diseases exhibit abnormalities in PCD pathways, drugs that can inhibit or modulate PCD may be critical in future therapeutic strategies. In this review, we briefly describe the process of various types of PCD and their roles in the occurrence and development of cardiovascular diseases. We also discuss the interplay between different cell death signaling cascades and summarize pharmaceutical agents targeting key players in cell death signaling pathways that have progressed to clinical trials. Ultimately a better understanding of PCD involved in cardiovascular diseases may lead to new avenues for therapy.
在各种心血管疾病的发生和发展过程中,可以观察到程序性细胞死亡(PCD)信号级联反应的异常,如凋亡、坏死、焦亡、铁死亡以及与自噬相关的细胞死亡。PCD途径的异常激活是导致心脏过度重塑和心力衰竭的共同特征,参与了各种心血管疾病的发病机制。相反,PCD的及时激活会以空间或时间受限的方式在损伤后重塑心脏结构和功能,并以类似的方式纠正心脏发育。由于许多心血管疾病在PCD途径中表现出异常,能够抑制或调节PCD的药物可能在未来的治疗策略中至关重要。在这篇综述中,我们简要描述了各种类型PCD的过程及其在心血管疾病发生和发展中的作用。我们还讨论了不同细胞死亡信号级联之间的相互作用,并总结了已进入临床试验阶段的针对细胞死亡信号通路关键分子的药物制剂。最终,对心血管疾病中PCD的更好理解可能会带来新的治疗途径。