Dabravolski Siarhei A, Kalmykov Vladislav A, Maksaeva Anastasia O, Rozhkova Ulyana V, Lapshina Ksenia O, Orekhov Alexander N
Department of Biotechnology Engineering, Braude Academic College of Engineering, Snunit 51, P.O. Box 78, 2161002, Karmiel, Israel.
Institute of General Pathology and Pathophysiology, 8 Baltiyskaya Street, Moscow, Russia, 125315.
Apoptosis. 2025 Mar 27. doi: 10.1007/s10495-025-02108-x.
Necroptosis is a programmed form of cell death that has gained significant attention in the field of cardiovascular research due to its involvement in myocardial infarction (MI) and myocardial ischaemia-reperfusion (I/R) injury. Unlike apoptosis, necroptosis elicits a pro-inflammatory response, contributing to myocardial injury, fibrosis, and adverse remodelling. This review aims to provide an overview of the molecular mechanisms underlying necroptosis, with a particular focus on its role in myocardial I/R injury. Key regulatory proteins such as Receptor-interacting protein kinase 3 (RIPK3) and Mixed lineage kinase domain-like protein (MLKL) are central to the necroptotic process, mediating cell death and inflammation. The review discusses the potential of targeting necroptosis as a therapeutic strategy for managing cardiovascular diseases, particularly post-MI. The RIPK3-CaMKII-mitochondrial permeability transition pore (mPTP) pathway is identified as a critical signalling axis in necroptosis and its inhibition may offer protective benefits in myocardial injury. The review also considers the role of natural and chemical inhibitors and other genes in necroptosis regulation. Overall, targeting necroptosis represents a promising avenue for therapeutic intervention to mitigate cardiac injury, promote recovery, and improve long-term patient outcomes in cardiovascular diseases.
坏死性凋亡是一种程序性细胞死亡形式，由于其参与心肌梗死（MI）和心肌缺血再灌注（I/R）损伤，在心血管研究领域受到了广泛关注。与凋亡不同，坏死性凋亡引发促炎反应，导致心肌损伤、纤维化和不良重塑。本综述旨在概述坏死性凋亡的分子机制，特别关注其在心肌I/R损伤中的作用。关键调节蛋白如受体相互作用蛋白激酶3（RIPK3）和混合谱系激酶结构域样蛋白（MLKL）是坏死性凋亡过程的核心，介导细胞死亡和炎症。本综述讨论了将靶向坏死性凋亡作为治疗心血管疾病（尤其是心肌梗死后）的治疗策略的潜力。RIPK3-CaMKII-线粒体通透性转换孔（mPTP）途径被确定为坏死性凋亡中的关键信号轴，抑制该途径可能对心肌损伤具有保护作用。本综述还考虑了天然和化学抑制剂以及其他基因在坏死性凋亡调节中的作用。总体而言，靶向坏死性凋亡是一种有前景的治疗干预途径，可减轻心脏损伤、促进恢复并改善心血管疾病患者的长期预后。
