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Low-Shear Stress Promotes Atherosclerosis via Inducing Endothelial Cell Pyroptosis Mediated by IKKε/STAT1/NLRP3 Pathway.
- Source :
-
Inflammation . Jun2024, Vol. 47 Issue 3, p1053-1066. 14p. - Publication Year :
- 2024
-
Abstract
- Atherosclerosis is initiated by vascular endothelial dysfunction, and low-shear stress (LSS) of blood flow is a key factor leading to endothelial dysfunction. Growing evidence suggests that endothelial cell pyroptosis plays an important role in the development of atherosclerosis. Studies have shown that low-shear stress can induce endothelial cell pyroptosis, but the exact mechanism remains unclear. Our experiments demonstrated that low-shear stress induced endothelial cell pyroptosis and the phosphorylation of IκB kinase ε (IKKε). IKKε knockdown not only significantly attenuated atherosclerosis lesions of aortic arch areas in ApoE−/− mice fed with high cholesterol diets, but also markedly reduced endothelial cell pyroptosis and NLRP3 expression triggered by low-shear stress. Further mechanism studies showed that IKKε promoted the expression of NLRP3 via activating signal transducer and activator of transcription 1 (STAT1) and the subsequent binding of STAT1 to NLRP3 promoter region. These results suggest that low-shear stress plays a pro-atherosclerotic role by promoting endothelial cell pyroptosis through the IKKε/STAT1/NLRP3 pathway, which provides new insights into the formation of atherosclerosis. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 03603997
- Volume :
- 47
- Issue :
- 3
- Database :
- Academic Search Index
- Journal :
- Inflammation
- Publication Type :
- Academic Journal
- Accession number :
- 177624717
- Full Text :
- https://doi.org/10.1007/s10753-023-01960-w