ArticlePloS one2012
Role of histone acetylation in the stimulatory effect of valproic acid on vascular endothelial tissue-type plasminogen activator expression.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 53 citations in OpenAlex.
- Novel histone deacetylase inhibitor, CS014, attenuates in vivo thrombosis while maintaining hemostasis.Journal of thrombosis and haemostasis : JTH · 2026Article
- Review
- Valproic Acid Inhibits RhoA-Mediated Vascular Smooth Muscle Cell Contraction.Journal of Korean medical science · 2025Article
- Exploration of effective biomarkers for venous thrombosis embolism in Behçet's disease based on comprehensive bioinformatics analysis.Scientific reports · 2024Article
- Zinc-Dependent Histone Deacetylases in Lung Endothelial Pathobiology.Biomolecules · 2024Review
- Valproate-Induced Metabolic Syndrome.Biomedicines · 2023Review
- The role of class IIa histone deacetylases in regulating endothelial function.Frontiers in physiology · 2023Review
- BDNF, proBDNF and IGF-1 serum levels in naïve and medicated subjects with autism.Scientific reports · 2022Article
- Targeting Histone Deacetylases in Idiopathic Pulmonary Fibrosis: A Future Therapeutic Option.Cells · 2022Review
- SARS-CoV-2 Infection, Sex-Related Differences, and a Possible Personalized Treatment Approach with Valproic Acid: A Review.Biomedicines · 2022Review
- Epigenetic evidence of an Ac/Dc axis by VPA and SAHA.Clinical epigenetics · 2021Article
- Valproic acid influences the expression of genes implicated with hyperglycaemia-induced complement and coagulation pathways.Scientific reports · 2021Article
- The Role of Histone Protein Acetylation in Regulating Endothelial Function.Frontiers in cell and developmental biology · 2021Review
- Histone Deacetylase Inhibitors: A Novel Strategy for Neuroprotection and Cardioprotection Following Ischemia/Reperfusion Injury.Journal of the American Heart Association · 2020Review
- Histone Deacetylases (HDACs) and Atherosclerosis: A Mechanistic and Pharmacological Review.Frontiers in cell and developmental biology · 2020Review
- Histone Deacetylase Inhibitors to Overcome Resistance to Targeted and Immuno Therapy in Metastatic Melanoma.Frontiers in cell and developmental biology · 2020Review
- Dual mechanisms for the regulation of brain-derived neurotrophic factor by valproic acid in neural progenitor cells.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2018Article
- Article
- Comparison of a teratogenic transcriptome-based predictive test based on human embryonic versus inducible pluripotent stem cells.Stem cell research & therapy · 2016Article
- Effect of Regulatory Element DNA Methylation on Tissue-Type Plasminogen Activator Gene Expression.PloS one · 2016Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsStimulated release of tissue-type plasminogen activator (t-PA) is pivotal for an intravascular fibrinolytic response and protects the circulation from occluding thrombosis. Hence, an impaired t-PA production is associated with increased risk for atherothrombotic events. A pharmacological means to stimulate the production of this enzyme may thus be desirable. We investigated if the anti-epileptic drug valproic acid (VPA) is capable of enhancing t-PA expression in vitro in vascular endothelial cells, and further examined if its histone deacetylase (HDAC)-inhibitory activity is of importance for regulating t-PA expression. METHODS AND
resultsHuman endothelial cells were exposed to valproic acid and t-PA mRNA and protein levels were quantified. Potential changes in histone acetylation status globally and at the t-PA promoter were examined by western blot and chromatin immunoprecipitation. Valproic acid dose-dependently stimulated t-PA mRNA and protein expression in endothelial cells reaching a 2-4-fold increase at clinically relevant concentrations and 10-fold increase at maximal concentrations. Transcription profiling analysis revealed that t-PA is selectively targeted by this agent. Augmented histone acetylation was detected at the t-PA transcription start site, and an attenuated VPA-response was observed with siRNA knock of HDAC3, HDAC5 and HDAC7.
conclusionsValproic acid induces t-PA expression in cultured endothelial cells, and this is associated with increased histone acetylation at the t-PA promoter. Given the apparent potency of valproic acid in stimulating t-PA expression in vitro this substance may be a candidate for pharmacological modulation of endogenous fibrinolysis in man.
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