Zhao Jiahao, Li Junli, Li Guoyong, Chen Mao
Laboratory of Heart Valve Disease, West China Hospital, Sichuan University, Chengdu, China.
Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, China.
Front Cardiovasc Med. 2022 Dec 14;9:1059576. doi: 10.3389/fcvm.2022.1059576. eCollection 2022.
Reactive oxygen species (ROS) metabolism is essential for the homeostasis of cells. Appropriate production of ROS is an important signaling molecule, but excessive ROS production can damage cells. ROS and ROS-associated proteins can act as damage associated molecular pattern molecules (DAMPs) to activate the NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome in cardiovascular diseases. Previous studies have shown that there are connected sites, termed mitochondria-associated membranes (MAMs), between mitochondria and the endoplasmic reticulum. In cardiovascular disease progression, MAMs play multiple roles, the most important of which is the ability to mediate ROS generation, which further activates the NLPR3 inflammasome, exacerbating the progression of disease. In this review, the following topics will be covered: 1. Molecular structures on MAMs that can mediate ROS generation; 2. Specific mechanisms of molecule-mediated ROS generation and the molecules' roles in cardiovascular disease, 3. The effects of MAMs-mediated ROS on the NLRP3 inflammasome in cardiovascular disease. The purpose of this review is to provide a basis for subsequent clinical treatment development.
活性氧(ROS)代谢对于细胞的稳态至关重要。适量产生的ROS是一种重要的信号分子,但过量产生ROS会损伤细胞。在心血管疾病中,ROS及与ROS相关的蛋白可作为损伤相关分子模式分子(DAMPs)激活含NACHT、LRR和PYD结构域的蛋白3(NLRP3)炎性小体。以往研究表明,线粒体与内质网之间存在称为线粒体相关膜(MAMs)的连接位点。在心血管疾病进展过程中,MAMs发挥多种作用,其中最重要的是介导ROS生成的能力,这会进一步激活NLPR3炎性小体,加剧疾病进展。在本综述中,将涵盖以下主题:1. MAMs上可介导ROS生成的分子结构;2. 分子介导ROS生成的具体机制及其在心血管疾病中的作用;3. MAMs介导的ROS对心血管疾病中NLRP3炎性小体的影响。本综述的目的是为后续临床治疗的发展提供依据。