ArticleProceedings of the National Academy of Sciences of the United States of America2021
Vitexin inhibits APEX1 to counteract the flow-induced endothelial inflammation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 63 citations in OpenAlex.
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- Targeting cytokine-like protein FAM3D alleviates atherosclerosis.Cell reports. Medicine · 2026Article
- Unraveling Atherosclerosis through Multi-omics: Systematic Insights into the Unique Applications and Clinical Perspectives.Current atherosclerosis reports · 2026Review
- miR-493-3p alleviates carotid artery stenosis by targeting YTHDF2.Journal of thrombosis and thrombolysis · 2026Article
- Narciclasine Alleviates Endothelial Inflammation and Atherosclerosis Initiation by Inhibiting Histone Lactylation-Mediated NF-κB Activation.Inflammation · 2026Article
- METTL3-mediated mApplied biochemistry and biotechnology · 2025Article
- Flavonoids for gastrointestinal tract local and associated systemic effects: A review of clinical trials and future perspectives.Journal of advanced research · 2025Review
- Epitranscriptomic sculpting: the role of mMedical oncology (Northwood, London, England) · 2025Review
- APEX1-STAT3 signaling mediates the force-coordinated endothelial regeneration.Cellular and molecular life sciences : CMLS · 2025Article
- Dietary Flavonoids Vitexin and Isovitexin: New Insights into Their Functional Roles in Human Health and Disease Prevention.International journal of molecular sciences · 2025Review
- METTL3: a multifunctional regulator in diseases.Molecular and cellular biochemistry · 2025Review
- From DNA Repair to Redox Signaling: The Multifaceted Role of APEX1 (Apurinic/Apyrimidinic Endonuclease 1) in Cardiovascular Health and Disease.International journal of molecular sciences · 2025Review
- Gastrointestinal absorption and its regulation of hawthorn leaves flavonoids.Scientific reports · 2025Article
- Review
- Strategies for arterial graft optimization at the single-cell level.Nature cardiovascular research · 2024Article
- Modulation of the vitamin D receptor by traditional Chinese medicines and bioactive compounds: potential therapeutic applications in VDR-dependent diseases.Frontiers in pharmacology · 2024Review
- Polyphenols targeting multiple molecular targets and pathways for the treatment of vitiligo.Frontiers in immunology · 2024Review
- Beneficial effects of flavonoids on animal models of atherosclerosis: A systematic review and meta-analysis.iScience · 2023Article
- Vitexin attenuates chronic kidney disease by inhibiting renal tubular epithelial cell ferroptosis via NRF2 activation.Molecular medicine (Cambridge, Mass.) · 2023Article
- Mechanobiology research in China.Mechanobiology in medicine · 2023Review
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Authors and funding
16 authors at 5 institutions in 2 countries.
Funding
Abstract
Vascular endothelial cells are exposed to shear stresses with disturbed vs. laminar flow patterns, which lead to proinflammatory vs. antiinflammatory phenotypes, respectively. Effective treatment against endothelial inflammation and the consequent atherogenesis requires the identification of new therapeutic molecules and the development of drugs targeting these molecules. Using Connectivity Map, we have identified vitexin, a natural flavonoid, as a compound that evokes the gene-expression changes caused by pulsatile shear, which mimics laminar flow with a clear direction, vs. oscillatory shear (OS), which mimics disturbed flow without a clear direction. Treatment with vitexin suppressed the endothelial inflammation induced by OS or tumor necrosis factor-α. Administration of vitexin to mice subjected to carotid partial ligation blocked the disturbed flow-induced endothelial inflammation and neointimal formation. In hyperlipidemic mice, treatment with vitexin ameliorated atherosclerosis. Using SuperPred, we predicted that apurinic/apyrimidinic endonuclease1 (APEX1) may directly interact with vitexin, and we experimentally verified their physical interactions. OS induced APEX1 nuclear translocation, which was inhibited by vitexin. OS promoted the binding of acetyltransferase p300 to APEX1, leading to its acetylation and nuclear translocation. Functionally, knocking down APEX1 with siRNA reversed the OS-induced proinflammatory phenotype, suggesting that APEX1 promotes inflammation by orchestrating the NF-κB pathway. Animal experiments with the partial ligation model indicated that overexpression of APEX1 negated the action of vitexin against endothelial inflammation, and that endothelial-specific deletion of APEX1 ameliorated atherogenesis. We thus propose targeting APEX1 with vitexin as a potential therapeutic strategy to alleviate atherosclerosis.
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