Abstract
Necrosis is an ancient topic which gains new attraction in the research area these years. There is no doubt that some necrosis can be regulated by genetic manipulation other than an accidental cell death resulting from physical or chemical stimuli. Recent advances in the molecular mechanism underlying the programmed necrosis show a fine regulation network which indicates new therapy targets in human diseases. Heart diseases seriously endanger our health and have high fatality rates in the patients. Cell death of cardiac myocytes is believed to be critical in the pathogenesis of heart diseases. Although necrosis is likely to play a more important role in cardiac cell death than apoptosis, apoptosis has been paid much attention in the past 30 years because it used to be considered as the only form of programmed cell death. However, recent findings of programmed necrosis and the related signalling pathways have broadened our horizon in the field of programmed cell death and promote new pharmacological application in the treatment of heart diseases. In this review, we summarize the advanced progress in these signalling pathways and discuss the pathos‐physiological relevance and therapeutic implication of targeting necrosis in heart diseases treatment.
Highlights
Numerous studies show that cardiac cell death is a major cause of heart diseases
In 2005, the concept that necrosis might occur in a regulated fashion was confirmed when researchers found molecules that inhibited receptor-interacting protein kinase 1 (RIP1) can protect cells from necrosis.[7]
Further study demonstrated the important role of Nec-1 in preventing adverse cardiac remodelling after myocardial ischaemia-reperfusion by necrosis inhibition through targeting RIP18,9 The discovery of kinase RIP3 and RIP1/RIP3 complex formation in necrosis induction had definitely determinate the concept of signalling-regulated necrosis or necroptosis.[10,11]
Summary
Numerous studies show that cardiac cell death is a major cause of heart diseases. Apoptosis and necrosis are 2 major modes of cardiac cell death and largely occurred in the pathogenesis process of heart diseases.[1].
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