Table3_Programmed Cell Death: Complex Regulatory Networks in Cardiovascular Disease.DOCX

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.

程序性细胞死亡（programmed cell death, PCD）信号通路异常可在多种心血管疾病的发生与进展过程中被观测到，涵盖细胞凋亡、细胞坏死、焦亡、铁死亡以及自噬相关细胞死亡等类型。程序性细胞死亡通路的异常激活是引发过度心肌重构与心力衰竭的常见特征，参与多种心血管疾病的发病进程。与之相对，在机体遭受损伤后，程序性细胞死亡的适时激活可在时空维度上受限地重塑心脏结构与功能，同时对心脏发育起到类似的正向调控作用。鉴于众多心血管疾病均存在程序性细胞死亡通路异常，能够抑制或调控程序性细胞死亡的药物或可成为未来治疗策略的关键方向。在本综述中，我们简要介绍各类程序性细胞死亡的过程及其在心血管疾病发生发展中的作用，同时探讨不同细胞死亡信号通路间的交互调控，并总结了靶向细胞死亡信号通路关键分子、已进入临床试验阶段的相关药物。最终，对参与心血管疾病的程序性细胞死亡机制的深入理解，有望为治疗开辟全新的研究路径。