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Updated: Apr 5, 2026
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Generation of a RIP1 Knockout U937 Cell Line Using the CRISPR-Cas9 System
Published on: April 11, 2025
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RIP3-mediated necrotic cell death accelerates systematic inflammation and mortality.
Lingjun Meng1, Wei Jin2, Xiaodong Wang3
1National Institute of Biological Sciences, Beijing 102206, China; College of Biological Sciences, China Agricultural University, Beijing 100094, China;
Summary
Receptor-interacting protein 3 (RIP3) activation drives programmed necrosis in atherosclerosis. Inhibiting RIP3 reduces inflammation, mitigates disease progression, and delays mortality in mice, suggesting a therapeutic target.
Area of Science:
- Cardiovascular Biology
- Immunology
- Cell Death Pathways
Background:
- Systemic inflammation is a key driver of cardiovascular disease, the leading global cause of mortality.
- The precise mechanisms initiating and sustaining inflammation in diseases like atherosclerosis remain incompletely understood.
- Programmed necrosis (necroptosis) is an inflammatory cell death pathway implicated in various diseases.
Purpose of the Study:
- To investigate the role of receptor-interacting protein 3 (RIP3) kinase and necroptosis in the pathogenesis of atherosclerosis.
- To determine the impact of RIP3 inhibition on inflammatory markers and disease severity in a mouse model.
- To explore the link between necroptosis, cytokine release, and monocyte recruitment in atherosclerotic lesions.
Main Methods:
- Utilized apolipoprotein E (ApoE)-knockout mice, including ApoE/RIP3 double-knockout models.
- Assessed RIP3 phosphorylation as a marker for necroptosis activation in atherosclerotic plaques.
- Quantified inflammatory cytokine mRNA expression, lymphocyte infiltration, and monocyte populations in blood and tissues.
Main Results:
- RIP3 phosphorylation, indicating necroptosis, was observed in atherosclerotic plaques of ApoE-knockout mice.
- ApoE/RIP3 double-knockout mice showed significantly decreased expression of inflammatory cytokines (e.g., IL-1α) in plaques.
- Lymphocyte infiltration and inflammatory monocyte levels were reduced, and mortality was significantly delayed in double-knockout mice compared to single knockouts.
Conclusions:
- RIP3-mediated necroptosis in atherosclerotic plaques contributes to systemic inflammation and disease exacerbation.
- Necrotic cell death may release cytokines that promote monocyte mobilization and lesion development.
- Targeting RIP3 and necroptosis presents a potential therapeutic strategy for cardiovascular disease.
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