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489

The pathophysiological role of receptor-interacting protein kinase 3 in cardiovascular disease

Jingjing Zhang1, Jianan Qian2, Wei Zhang3

  • 1School of Medicine, Nantong University, Nantong, Jiangsu 226001, China.

Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie
|June 17, 2023
PubMed

Insights

Receptor interacting protein kinase 3 (RIPK3) drives myocardial necroptosis by affecting CaMK II and mitochondrial pores. Inhibiting RIPK3 shows promise for treating cardiovascular diseases.

Area of Science:

  • Cardiovascular Biology
  • Cell Death Mechanisms
  • Molecular Cardiology

Background:

  • Receptor interacting protein kinase 3 (RIPK3) is implicated in necroptosis, a form of programmed cell death.
  • RIPK3 mediates CaMK II phosphorylation/oxidation, opening the mitochondrial permeability transition pore (mPTP), and inducing myocardial necroptosis.
  • Necroptosis is increasingly recognized for its role in cardiovascular disease pathogenesis.

Purpose of the Study:

  • To review the current understanding of RIPK3's role in necroptosis, inflammation, and oxidative stress.
  • To discuss the involvement of RIPK3 in various cardiovascular diseases.
  • To highlight RIPK3 as a potential therapeutic target for cardiovascular conditions.

Main Methods:

  • Literature review of studies investigating RIPK3 function and its role in cardiovascular diseases.
  • Analysis of molecular mechanisms linking RIPK3 to CaMK II, mPTP opening, and necroptosis.
  • Examination of evidence for RIPK3 inhibition in preclinical models of cardiovascular disease.

Main Results:

  • Increased RIPK3 expression or phosphorylation are key markers of necroptosis.
  • Inhibition of CaMK II phosphorylation/oxidation significantly reduces RIPK3-mediated myocardial necroptosis.
  • The RIPK3 inhibitor GSK’872 effectively inhibits cardiovascular disease progression and reverses associated cardiac dysfunction.

Conclusions:

  • RIPK3 is a critical mediator of myocardial necroptosis and plays a significant role in cardiovascular diseases.
  • Targeting RIPK3, for example with GSK’872, offers a potential therapeutic strategy for cardiovascular diseases.
  • Further research into RIPK3's functions may uncover new avenues for treating conditions like atherosclerosis, myocardial ischemia, infarction, and heart failure.
Keywords:
Cardiovascular diseasesInflammationMyocardial hypertrophyNecroptosisOxidative stressReceptor interacting protein kinase 3 (RIPK3)

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