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Review
. 2022 Oct;27(9-10):697-719.
doi: 10.1007/s10495-022-01760-x. Epub 2022 Aug 20.

The regulation of necroptosis and perspectives for the development of new drugs preventing ischemic/reperfusion of cardiac injury

Leonid N Maslov  1   2 , Sergey V Popov  3 , Natalia V Naryzhnaya  3 , Alexandr V Mukhomedzyanov  3 , Boris K Kurbatov  3 , Ivan A Derkachev  3 , Alla A Boshchenko  3 , Igor Khaliulin  4   5 , N Rajendra Prasad  6 , Nirmal Singh  7 , Alexei Degterev  8 , Evgenia A Tomilova  9 , Ekaterina V Sapozhenkova  9
Affiliations
Review

The regulation of necroptosis and perspectives for the development of new drugs preventing ischemic/reperfusion of cardiac injury

Leonid N Maslov et al. Apoptosis. 2022 Oct.

Abstract

In the last 10 years, mortality from acute myocardial infarction (AMI) has not significantly decreased. This situation is associated with the absence in clinical practice of highly effective drugs capable of preventing the occurrence of reperfusion injury of the heart. Necroptosis inhibitors may become prototypes for the creation of highly effective drugs that increase cardiac tolerance to ischemic/reperfusion (I/R) and reduce the mortality rate in patients with AMI. Necroptosis is involved in I/R cardiac injury and inhibition of RIPK1 or RIPK3 contributes to an increase in cardiac tolerance to I/R. Necroptosis could also be involved in the development of adverse remodeling of the heart. It is unclear whether pre- and postconditioning could inhibit necroptosis of cardiomyocytes and endothelial cells. The role of necroptosis in coronary microvascular obstruction and the no-reflow phenomenon also needs to be studied. MicroRNAs and LncRNAs can regulate necroptotic cell death. Ca2+ overload and reactive oxygen species could be the triggers of necroptosis. Activation of kinases (p38, JNK1, Akt, and mTOR) could promote necroptotic cell death. The interaction of necroptosis, apoptosis, autophagy, ferroptosis, and pyroptosis is discussed. The water-soluble necroptosis inhibitors may be highly effective drugs for treatment of AMI or stroke. It is possible that microRNAs may become the basis for creating drugs for treatment of diseases triggered by I/R of organs.

Keywords: Heart; Ischemia; Kinases; Necroptosis; Reactive oxygen species; Reperfusion; microRNAs.

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