ArticleClinical and translational medicine2025
Disturbed shear stress promotes atherosclerosis through TRIM21-regulated MAPK6 degradation and consequent endothelial inflammation.
Article in Clinical and translational medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 1 of them a synthesis that pooled it.
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Who cites it
7 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Mechanopriming by vascular stiffness and phenotypic reprogramming by disturbed flow: mechanobiology and clinical translation in atherosclerosis.Frontiers in cardiovascular medicine · 2026Pooled it
- Extracellular signal-regulated kinase 3 forms a nuclear complex with Aly/REF export factor and the splicing factor proline and glutamine rich to exacerbate pathological cardiac remodeling due to pressure overload.Molecular biomedicine · 2026Article
- Phase Separation of TRIM21 Modulates PTPN14 Stability to Drive Flow-Dependent Endothelial Activation and Atherogenesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Emerging Role and Potential Therapeutic Application of TRIM Proteins in Cardiovascular Diseases.Biomolecules · 2026Review
- Potential active ingredients and mechanisms of Shufeitie ointment in the treatment of chronic obstructive pulmonary disease by integrating transdermal chemistry and network pharmacology.Frontiers in medicine · 2025Article
- Ubiquitination-mediated protein homeostasis in cardiovascular diseases: molecular mechanisms and therapeutic opportunities.American journal of cardiovascular disease · 2025Review
- Disturbed shear stress promotes atherosclerosis through TRIM21-regulated MAPK6 degradation and consequent endothelial inflammation.Clinical and translational medicine · 2025Article
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Authors and funding
13 authors.
Funding
Abstract
rationaleCoronary artery plaques often develop in regions subjected to disturbed shear stress (DSS), yet the mechanisms underlying this phenomenon remain poorly understood. Our study aimed to elucidate the unknown role of MAPK6 in shear stress and plaque formation.
methodsIn vitro and in vivo experiments, RNA-seq, CO-IP and proteomic analysis, combined with single-cell RNA-seq datasets were used to reveal the upstream and downstream mechanisms involved. AAV-MAPK6, ApoE
resultsOur study revealed a substantial decrease in MAPK6 protein levels in endothelial cells in response to DSS, both in vivo and in vitro, which was contingent on the binding of the ubiquitin ligase TRIM21 to MAPK6. Endothelium-specific MAPK6 overexpression exerts antiatherosclerotic effects in ApoE
conclusionsOur study illuminates the advantages of MAPK6 in decelerating plaque progression, highlighting the potential of safeguarding MAPK6 as a novel therapeutic strategy against atherosclerosis. KEY POINTS: 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.
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