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Lookup NU author(s): Professor Fiona OakleyORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© The Author(s) 2025. Published by Oxford University Press on behalf of the European Society of Cardiology.Aims Atherosclerosis initiation at sites of disturbed blood flow involves heightened inflammation coupled to excessive endothelial cell (EC) proliferation. Here, we unveil the pivotal role of c-REL, a member of the NF-κB transcription factor family, in orchestrating these processes by driving dual pathological inflammatory and cell cycle pathways. Methods and results Analysis of cultured EC and murine models revealed enrichment and activation of c-REL at atherosusceptible sites experiencing disturbed flow. Transcriptome analysis, extensively validated in vitro and in vivo, demonstrates that endothelial c-REL drives inflammation via a TXNIP-p38 MAP kinase signalling pathway and enhances proliferation through a non-canonical NFKB2-p21 pathway. Consistent with its pivotal role in EC pathology, genetic deletion of c-Rel in EC significantly reduces plaque burden in hypercholesterolaemic mice. Conclusion These findings underscore the fundamental role of c-REL in endothelial responses to disturbed flow and highlight therapeutic targeting of endothelial c-REL as a potential strategy for atherosclerosis treatment.
Author(s): Tardajos Ayllon B, Bowden N, Souilhol C, Darwish H, Tian S, Duckworth C, Pritchard DM, Xu S, Sayers J, Francis S, Serbanovic-Canic J, Oakley F, Evans PC
Publication type: Article
Publication status: Published
Journal: Cardiovascular Research
Year: 2025
Volume: 121
Issue: 5
Pages: 748-759
Print publication date: 01/04/2025
Online publication date: 21/02/2025
Acceptance date: 07/01/2025
Date deposited: 10/06/2025
ISSN (print): 0008-6363
ISSN (electronic): 1755-3245
Publisher: Oxford University Press
URL: https://doi.org/10.1093/cvr/cvaf024
DOI: 10.1093/cvr/cvaf024
Data Access Statement: The data underlying this article are available in the article and in its online supplementary material
PubMed id: 39982773
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