ArticleArteriosclerosis, thrombosis, and vascular biology2011
p53 impairs endothelial function by transcriptionally repressing Kruppel-Like Factor 2.
Article in Arteriosclerosis, thrombosis, and vascular biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 74 citations in OpenAlex.
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- Myocardial infarction induces endothelial dysfunction with independence of cardiovascular risk factors.Angiogenesis · 2025Article
- HPV16 E6 and E7 expressing cancer cells suppress the antitumor immune response by upregulating KLF2-mediated IL-23 expression in macrophages.Journal for immunotherapy of cancer · 2025Article
- Restoration of NOX4 signalling reverses endothelial colony-forming cell angiogenic dysfunction associated with experimental and clinical diabetes.Stem cell research & therapy · 2025Article
- The COVID-19 thrombus: distinguishing pathological, mechanistic, and phenotypic features and management.Journal of thrombosis and thrombolysis · 2025Review
- Plxnd1-mediated mechanosensing of blood flow controls the caliber of the Dorsal Aorta via the transcription factor Klf2.bioRxiv : the preprint server for biology · 2024Article
- Immune cell-mediated venous thrombus resolution.Research and practice in thrombosis and haemostasis · 2023Review
- The adverse effect of anticancer drug toremifene on vascular smooth muscle cells is an important aspect of its tumor growth inhibition.Journal of cancer research and clinical oncology · 2023Article
- DNA damage response signaling: A common link between cancer and cardiovascular diseases.Cancer medicine · 2023Review
- Review
- Bioinformatics Analysis of Common Genetic and Molecular Traits and Association of Portal Hypertension with Pulmonary Hypertension.Journal of healthcare engineering · 2022Article
- The role of p53 in the alternation of vascular functions.Frontiers in pharmacology · 2022Review
- Cardiovascular Benefits from Gliflozins: Effects on Endothelial Function.Biomedicines · 2021Review
- A pro-inflammatory mediator USP11 enhances the stability of p53 and inhibits KLF2 in intracerebral hemorrhage.Molecular therapy. Methods & clinical development · 2021Article
- Angiotensin II-induced upregulation of SGLT1 and 2 contributes to human microparticle-stimulated endothelial senescence and dysfunction: protective effect of gliflozins.Cardiovascular diabetology · 2021Article
- Resolution of Deep Venous Thrombosis: Proposed Immune Paradigms.International journal of molecular sciences · 2020Review
- Empagliflozin improved systolic blood pressure, endothelial dysfunction and heart remodeling in the metabolic syndrome ZSF1 rat.Cardiovascular diabetology · 2020Article
- Angiotensin II-induced redox-sensitive SGLT1 and 2 expression promotes high glucose-induced endothelial cell senescence.Journal of cellular and molecular medicine · 2020Article
- The Role of Protein SUMOylation in the Pathogenesis of Atherosclerosis.Journal of clinical medicine · 2019Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
objectiveTo evaluate if p53 decreases Kruppel-Like Factor 2 (KLF2) expression and determine whether p53-mediated suppression of KLF2 plays a role in p53-induced endothelial dysfunction. METHODS AND
resultsEndothelial KLF2 mediates endothelium-dependent vascular homeostasis by differentially regulating endothelial genes, leading to an anti-inflammatory and antithrombotic endothelial surface with normal vasodilatory function. In contrast, the tumor suppressor p53 leads to inflammatory gene expression and impairs endothelium-dependent vasodilatation, thus promoting endothelial dysfunction. The effect of p53 on KLF2 expression was determined. p53 inhibited KLF2 transcription in a histone deacetylase-dependent and a histone acetyltransferase-independent fashion. KLF2 expression was suppressed by p53 via a conserved p53-binding repressor sequence in its promoter. p53 bound to, and stimulated, deacetylation of Histone H3 at the KLF2 promoter. The effect of p53 on endothelial KLF2 target genes was examined. Downregulation of p53 increased expression of endothelial NO synthase and thrombomodulin and inhibited expression of plasminogen activator inhibitor 1. Conversely, overexpression of p53 suppressed endothelial NO synthase and thrombomodulin expression and stimulated plasminogen activator inhibitor 1 and endothelin-1 expression. Knockdown of KLF2 abolished the p53-induced decrease in thrombomodulin and increase in endothelin-1. Both, overexpression of p53 and knockdown of KLF2 in endothelial cells increased blood coagulation on an endothelial cell monolayer. The p53-induced increase in coagulation was rescued by forced expression of KLF2. p53 also impaired endothelium-dependent vasodilatation and decreased bioavailable vascular NO, both of which were rescued by forced KLF2 expression.
conclusionsThese findings illustrate a novel p53-dependent mechanism for the regulation of endothelial KLF2 expression. In addition, they show that downregulation of KLF2, in part, mediates a p53-stimulated dysfunctional endothelium.
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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.