Programmed Cell Death: Complex Regulatory Networks in Cardiovascular Disease.

Liuhua Zhou,Tongtong Yang,Hao Wang,Liansheng Wang,Lingfeng Gu,Tiankai Shan,Jiateng Sun,Sibo Wang,Tianwen Wei

doi:10.3389/fcell.2021.794879

Abstract

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.

Highlights

The development and homeostasis of multicellular organisms depend on the regulation of cell survival and renewal, and on the processing of those cells that are no longer needed or pose a potential danger to the organism
While research into cardiovascular disease has focused on the molecular mechanisms of individual Programmed cell death (PCD) types, it is clear that different PCD pathways do not operate in isolation
A more likely explanation basing on current knowledge about the various possibilities of triggering and reconnecting PCD signaling cascades suggests that autophagy, apoptosis, ferroptosis, pyroptosis, and necrosis constitute a pluralistic, coordinated cell death system in which one pathway can flexibly compensate for the other (Konstantinidis et al., 2012; Tower, 2015; Wang and Kanneganti, 2021)

Summary

Introduction

The development and homeostasis of multicellular organisms depend on the regulation of cell survival and renewal, and on the processing of those cells that are no longer needed or pose a potential danger to the organism.

Results

Conclusion