ArticleJournal of translational medicine2019
Atheroprotective effects of methotrexate via the inhibition of YAP/TAZ under disturbed flow.
Article in Journal of translational medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 41 citations in OpenAlex.
- Targeting endoplasmic reticulum stress and YAP/TAZ-SMAD1/5 signaling to ameliorate endothelial dysfunction in diabetes.Acta pharmacologica Sinica · 2026Article
- Endothelial-to-mesenchymal transition in atherosclerosis: mechanisms, therapeutic targets, and future perspectives.Frontiers in cell and developmental biology · 2026Review
- Vascular Mechanobiology: From Membrane to Nucleus.Advances in experimental medicine and biology · 2026Review
- Reconceptualizing Endothelial-to-mesenchymal transition in atherosclerosis: Signaling pathways and prospective targeting strategies.Journal of advanced research · 2025Review
- YAP/TAZ as mechanobiological signaling pathway in cardiovascular physiological regulation and pathogenesis.Mechanobiology in medicine · 2024Article
- Recent advances of mechanosensitive genes in vascular endothelial cells for the formation and treatment of atherosclerosis.Genes & diseases · 2024Review
- Mechanotransduction of the vasculature in Hutchinson-Gilford Progeria Syndrome.Frontiers in physiology · 2024Review
- Molecular Linkage between Immune System Disorders and Atherosclerosis.Current issues in molecular biology · 2023Review
- YAP/TAZ: Molecular pathway and disease therapy.MedComm · 2023Review
- Endothelial mechanobiology in atherosclerosis.Cardiovascular research · 2023Review
- Candidate SNP Markers Significantly Altering the Affinity of TATA-Binding Protein for the Promoters of Human Hub Genes for Atherogenesis, Atherosclerosis and Atheroprotection.International journal of molecular sciences · 2023Article
- Mendelian Randomization Analysis Reveals Statins Potentially Increase Amyotrophic Lateral Sclerosis Risk Independent of Peripheral Cholesterol-Lowering Effects.Biomedicines · 2023Article
- Vascular mechanotransduction.Physiological reviews · 2023Review
- The Clinical Significance of Salusins in Systemic Sclerosis-A Cross-Sectional Study.Diagnostics (Basel, Switzerland) · 2023Article
- The actions of methotrexate on endothelial cells are dependent on the shear stress-induced regulation of one carbon metabolism.Frontiers in immunology · 2023Article
- The Impact of Cytokines in Coronary Atherosclerotic Plaque: Current Therapeutic Approaches.International journal of molecular sciences · 2022Review
- G3BP2 regulates oscillatory shear stress-induced endothelial dysfunction.Genes & diseases · 2022Article
- Methotrexate improves endothelial function in early rheumatoid arthritis patients after 3 months of treatment.Arthritis research & therapy · 2022Article
- Mechanical regulation of chromatin and transcription.Nature reviews. Genetics · 2022Review
- The regulation of yes-associated protein/transcriptional coactivator with PDZ-binding motif and their roles in vascular endothelium.Frontiers in cardiovascular medicine · 2022Review
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Authors and funding
16 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAtherosclerosis preferentially develops in regions of disturbed flow (DF). Emerging evidence indicates that yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ), which are both effectors of the Hippo pathway, sense different blood flow patterns and regulate atherosclerotic lesions. We previously found that methotrexate (MTX) reduces in-stent neoatherosclerosis, decreases the plaque burden, and has an effect on local fluid shear stress. Here, we investigated the atheroprotective effect of MTX under DF and the mechanisms underlying these properties.
methodsHuman umbilical vein endothelial cells (HUVECs) were subjected to biomechanical stretch using a parallel-plate flow system and treated with or without MTX at therapeutically relevant concentrations. Additionally, an extravascular device was used to induce DF in the left common carotid artery of C57BL/6 mice, followed by treatment with MTX or 0.9% saline. The artery was then assessed histopathologically after 4 weeks on a Western diet.
resultsWe observed that MTX significantly inhibited DF-induced endothelial YAP/TAZ activation. Furthermore, it markedly decreased pro-inflammatory factor secretion and monocyte adhesion in HUVECs but had no effect on apoptosis. Mechanistically, AMPKa1 depletion attenuated these effects of MTX. Accordingly, MTX decreased DF-induced plaque formation, which was accompanied by YAP/TAZ downregulation in vivo.
conclusionsTaken together, we conclude that MTX exerts protective effects via the AMP-dependent kinase (AMPK)-YAP/TAZ pathway. These results provide a basis for the prevention and treatment of atherosclerosis via the inhibition of YAP/TAZ.
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