ArticleAngiogenesis2016
The decrease in histone methyltransferase EZH2 in response to fluid shear stress alters endothelial gene expression and promotes quiescence.
Article in Angiogenesis, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 3 of them syntheses that pooled it.
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Who cites it
55 citing papers in PubMed, 3 syntheses or guidelines pooled it, 82 citations in OpenAlex.
- Histone modification of endothelial-mesenchymal transition in cardiovascular diseases.Frontiers in cardiovascular medicine · 2022Pooled it
- Targeting epigenetics and non-coding RNAs in atherosclerosis: from mechanisms to therapeutics.Pharmacology & therapeutics · 2019Pooled it
- Unfolding the pathogenesis of scleroderma through genomics and epigenomics.Journal of autoimmunity · 2017Pooled it
- Article
- Polycomb Repressive Complex 2 drives flow-sensitive endothelial states underlying vascular inflammation and disease.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Epigenetic regulation in atherosclerosis and its therapeutic potential.Nature reviews. Cardiology · 2026Review
- Stress fiber traction force reshapes chromatin accessibility and YAP binding to direct diverse transcriptional programs in mesenchymal stem cells.Mechanobiology in medicine · 2026Article
- Endothelial Metabolic Reprogramming Links Diabetes to Atherosclerosis.Diabetes, metabolic syndrome and obesity : targets and therapy · 2026Review
- NDRG1 as a sensor and mediator of endothelial stress: from homeostasis to inflammation and cardiovascular disease.Cellular and molecular life sciences : CMLS · 2025Review
- Revealing the biophysics of lamina-associated domain formation by integrating theoretical modeling and high-resolution imaging.Nature communications · 2025Article
- cSTAR analysis identifies endothelial cell cycle as a key regulator of flow-dependent artery remodeling.Science advances · 2025Article
- Latrophilin-2 mediates fluid shear stress mechanotransduction at endothelial junctions.The EMBO journal · 2024Article
- N6-methyladenosine modification of KLF2 may contribute to endothelial-to-mesenchymal transition in pulmonary hypertension.Cellular & molecular biology letters · 2024Article
- Shear-Sensitive circRNA-LONP2 Promotes Endothelial Inflammation and Atherosclerosis by Targeting NRF2/HO1 Signaling.JACC. Basic to translational science · 2024Article
- Repressive H3K27me3 drives hyperglycemia-induced oxidative and inflammatory transcriptional programs in human endothelium.Cardiovascular diabetology · 2024Article
- H3K27Me3 abundance increases fibrogenesis during endothelial-to-mesenchymal transition via the silencing of microRNA-29c.Frontiers in cardiovascular medicine · 2024Article
- Endothelial-to-mesenchymal transition: An underappreciated mediator of diabetic complications.Frontiers in endocrinology · 2023Review
- Endothelial β-arrestins regulate mechanotransduction by the type II bone morphogenetic protein receptor in primary cilia.Pulmonary circulation · 2022Article
- KLF4 recruits SWI/SNF to increase chromatin accessibility and reprogram the endothelial enhancer landscape under laminar shear stress.Nature communications · 2022Article
- Histone demethylase JMJD3 downregulation protects against aberrant force-induced osteoarthritis through epigenetic control of NR4A1.International journal of oral science · 2022Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
High uniform fluid shear stress (FSS) is atheroprotective and preserves the endothelial phenotype and function through activation of downstream mediators such as MAPK7 (Erk5). Endothelial cells respond to FSS thanks to mechanotransduction. However, how the resulting signaling is integrated and resolved at the epigenetic level remains elusive. We hypothesized that Polycomb methyltransferase EZH2 is involved in the effects of FSS in human endothelial cells. We showed that FSS decreases the expression of the Polycomb methyltransferase EZH2. Despite simultaneous activation of MAPK7, MAPK7 pathway does not directly influence the transcription of EZH2. Interestingly though, the knockdown of EZH2 activates the protective MAPK7 signaling in endothelial cells, even in the absence of FSS. To understand the influence of the FSS-decreased expression of EZH2 on endothelial transcriptome, we performed RNA-seq and differential gene expression analysis. We identified candidate groups of genes dependent on both EZH2 and FSS. Among those, Gene Ontology overrepresentation analysis revealed highly significant enrichment of the cell cycle-related genes, suggesting changes in proliferation. Indeed, the depletion of EZH2 strongly inhibited endothelial proliferation, indicating cell cycle arrest. The concomitant decrease in CCNA expression suggests the transition of endothelial cells into a quiescent phenotype. Further bioinformatical analysis suggested TXNIP as a possible mediator between EZH2 and cell cycle-related gene network. Our data show that EZH2 is a FSS-responsive gene. Decreased EZH2 levels enhance the activation of the atheroprotective MAPK7 signaling. Decrease in EZH2 under FSS mediates the decrease in the expression of the network of cell cycle-related genes, which allows the cells to enter quiescence. EZH2 is therefore important for the protective effects of FSS in endothelium.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.