Related Experiment Video

Updated: Jun 11, 2026

Generation of a RIP1 Knockout U937 Cell Line Using the CRISPR-Cas9 System
08:15

Generation of a RIP1 Knockout U937 Cell Line Using the CRISPR-Cas9 System

Published on: April 11, 2025

Receptor-interacting protein kinases (RIPK1-RIPK4) in cardiac pathophysiology: Mechanistic signaling, disease

Basma Refai Ali Mohamed1, Mengdie Wang1, Jiafeng Xie2

  • 1Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan, Guangdong 528400, China; Stake Key Laboratory of Chemical Biology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; University of Chinese Academy of Sciences, Beijing 101408, China.

Pharmacological Research
|June 9, 2026
PubMed

Insights

Receptor-interacting protein kinases (RIPKs) are key in heart disease, regulating cell death and inflammation. This review details RIPK roles in cardiac pathologies and explores therapeutic strategies targeting these kinases.

Area of Science:

  • Cardiovascular Biology
  • Molecular Medicine
  • Cell Death Signaling

Background:

  • Receptor-interacting protein kinases (RIPKs) are crucial for innate immunity, inflammation, and regulated cell death.
  • Dysregulated RIPK signaling is increasingly linked to cardiomyocyte injury, fibrosis, and maladaptive remodeling in cardiovascular disease.
  • While RIPK1 and RIPK3 roles in necroptosis are known, RIPKs have broader non-canonical functions in cardiac pathologies.

Purpose of the Study:

  • To provide an updated overview of RIPK1-RIPK4 signaling in cardiovascular disease.
  • To emphasize both canonical necroptotic and non-canonical signaling mechanisms of RIPKs in the heart.
  • To summarize therapeutic strategies and highlight knowledge gaps for RIPK-targeted therapies in cardiac conditions.

Main Methods:

  • Literature review of preclinical and clinical studies on RIPKs in cardiovascular disease.
  • Analysis of RIPK involvement in various cardiac pathologies including ischemia/reperfusion injury, heart failure, and cardiomyopathy.
  • Synthesis of information on therapeutic approaches and translational challenges.

Main Results:

  • RIPKs play significant roles in myocardial ischemia/reperfusion injury, heart failure, cardiac hypertrophy, diabetic cardiomyopathy, myocarditis, and doxorubicin-induced cardiotoxicity.
  • RIPK1-4 signaling impacts cardiomyocyte injury, fibrosis, mitochondrial dysfunction, and inflammation.
  • Emerging evidence highlights RIPK2 in sterile cardiac inflammation and RIPK4 in oxidative stress responses.

Conclusions:

  • RIPKs are critical mediators in diverse cardiovascular diseases through both canonical and non-canonical pathways.
  • Targeting RIPKs presents a promising therapeutic avenue for various cardiac conditions.
  • Further research is needed to address isoform-specific functions, temporal dynamics, and clinical translation challenges.
Keywords:
Cardiovascular diseaseInflammationMitochondrial dysfunctionNecroptosisOxidative stressRIP kinases

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