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

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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.

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Data availability

The datasets analysed during the current study are available in the PubMed repository.

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Funding

This article was supported by state assignment (Grant No.122020300042-4).

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Authors and Affiliations

  1. Cardiology Research Institute, Tomsk National Research Medical Centre, The Russian Academy of Sciences, Tomsk, Russia

    Leonid N. Maslov, Sergey V. Popov, Natalia V. Naryzhnaya, Alexandr V. Mukhomedzyanov, Boris K. Kurbatov, Ivan A. Derkachev & Alla A. Boshchenko

  2. Institute for Drug Research, School of Pharmacy, Faculty of Medicine, Hebrew University of Jerusalem, Pharmacy Building, Ein Karem, 91120, Jerusalem, Israel

    Igor Khaliulin

  3. Bristol Medical School (THS), Faculty of Health Sciences, University of Bristol, Bristol Royal Infirmary, Upper Maudlin Street, Bristol, BS2 8HW, UK

    Igor Khaliulin

  4. Department of Biochemistry and Biotechnology, Annamalai University, Annamalainagar, Tamil Nadu, India

    N. Rajendra Prasad

  5. Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, India

    Nirmal Singh

  6. Department of Developmental, Molecular and Chemical Biology, Tufts University School of Medicine, Boston, MA, USA

    Alexei Degterev

  7. Tyumen State Medical University, Tyumen, Russia

    Evgenia A. Tomilova & Ekaterina V. Sapozhenkova

  8. Laboratory of Experimental Cardiology, Cardiology Research Institute, Tomsk National Research Medical Center of the RAS, Kyevskaya 111A, Tomsk, Russia, 634012

    Leonid N. Maslov

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  1. Leonid N. Maslov
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SVP verification of critical intellectual content, article editing. AVM, BKK and IAD searching for published data on the subject of an article, writing and typing of articles, preparation for publishing and preparing figures. AAB, NVN, IK, NRP, NS, AD, EAT and EVS verification of critical intellectual content. LNM devised the project, the main conceptual ideas of the article, final approval of the content for publication of the manuscript. All authors read and approved the final manuscript.

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Maslov, L.N., Popov, S.V., Naryzhnaya, N.V. et al. The regulation of necroptosis and perspectives for the development of new drugs preventing ischemic/reperfusion of cardiac injury. Apoptosis 27, 697–719 (2022). https://doi.org/10.1007/s10495-022-01760-x

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