Disturbed shear stress promotes atherosclerosis through TRIM21-regulated MAPK6 degradation and consequent endothelial inflammation

Feng Wang; Shu-Yu Wang; Yue Gu; Shuai Luo; Ai-Qun Chen; Chao-Hua Kong; Wen-Ying Zhou; Li-Guo Wang; Zhi-Mei Wang; Guang-Feng Zuo; Xiao-Fei Gao; Jun-Jie Zhang; Shao-Liang Chen

doi:10.1002/ctm2.70168

Clinical and Translational Medicine ›› 2025, Vol. 15 ›› Issue (1) : e70168 DOI: 10.1002/ctm2.70168

RESEARCH ARTICLE

Disturbed shear stress promotes atherosclerosis through TRIM21-regulated MAPK6 degradation and consequent endothelial inflammation

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Abstract

	•Disturbed flow activates the ubiquitin‒proteasome degradation pathway of MAPK6 in endothelial cells, which is contingent on the binding of the ubiquitin ligase TRIM21 to MAPK6.
	•Endothelial MAPK6 has an advantageous impact on decelerating plaque progression.
	•MAPK6 regulates endothelial inflammation via the EGR1/CXCL12 axis.

Keywords

atherosclerosis / endothelial inflammation / MAPK6 / shear stress / TRIM21

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Feng Wang, Shu-Yu Wang, Yue Gu, Shuai Luo, Ai-Qun Chen, Chao-Hua Kong, Wen-Ying Zhou, Li-Guo Wang, Zhi-Mei Wang, Guang-Feng Zuo, Xiao-Fei Gao, Jun-Jie Zhang, Shao-Liang Chen. Disturbed shear stress promotes atherosclerosis through TRIM21-regulated MAPK6 degradation and consequent endothelial inflammation. Clinical and Translational Medicine, 2025, 15(1): e70168 DOI:10.1002/ctm2.70168

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2025 The Author(s). Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.