Necroptosis in myocardial ischaemia-reperfusion injury: current update on mechanisms, therapeutic targets, and translational potential

被引:0
|
作者
Dabravolski, Siarhei A. [1 ]
Kalmykov, Vladislav A. [2 ]
Maksaeva, Anastasia O. [2 ,3 ]
Rozhkova, Ulyana V. [2 ]
Lapshina, Ksenia O. [4 ]
Orekhov, Alexander N. [4 ]
机构
[1] Braude Acad Coll Engn, Dept Biotechnol Engn, Snunit 51,POB78, IL-2161002 Karmiel, Israel
[2] Inst Gen Pathol & Pathophysiol, 8 Baltiyskaya St, Moscow 125315, Russia
[3] Sechenov First Moscow State Med Univ, 8 Trubetskaya St,Bldg 2, Moscow 119991, Russia
[4] Natl Res Univ Higher Sch Econ, Fac Biol & Biotechnol, 33 Profsoyuznaya St,Bldg 4, Moscow 117418, Russia
基金
俄罗斯科学基金会;
关键词
Necroptosis; Myocardial infarction; Ischaemia-reperfusion injury; Cardiac damage; RIPK3-MLKL pathway; RIPK3; inhibitors; MOLECULAR-MECHANISMS; INFARCTION; APOPTOSIS; AUTOPHAGY; STRESS; PATHOPHYSIOLOGY; INHIBITION; ACTIVATION; MORTALITY; ADENOSINE;
D O I
10.1007/s10495-025-02108-x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
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页数:19
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