ArticleFrontiers in pharmacology2018
Valproic Acid Induces Endothelial-to-Mesenchymal Transition-Like Phenotypic Switching.
Article in Frontiers in pharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 32 citations in OpenAlex.
- ATG7 vs. ATG5: Distinct autophagy pathways shaping TGF-β signaling and endothelial function.PloS one · 2026Article
- Valproic Acid Inhibits RhoA-Mediated Vascular Smooth Muscle Cell Contraction.Journal of Korean medical science · 2025Article
- Shifting Shapes: The Endothelial-to-Mesenchymal Transition as a Driver for Cancer Progression.International journal of molecular sciences · 2025Review
- Endothelial-to-Mesenchymal Transition in Cardiovascular Pathophysiology.International journal of molecular sciences · 2024Review
- Protein Disulfide Isomerase 4 Is an Essential Regulator of Endothelial Function and Survival.International journal of molecular sciences · 2024Article
- MicroRNA miR-378-3p is a novel regulator of endothelial autophagy and function.Journal of molecular and cellular cardiology plus · 2023Article
- Tumors derived from lung cancer cells respond differently to treatment with sodium valproate (a HDAC inhibitor) in a chicken embryo chorioallantoic membrane model.Histology and histopathology · 2022Article
- [Valproic Acid Could Help in the Fight Against COVID-19: a case-control study].Neurologia (Barcelona, Spain) · 2022Article
- Pravastatin-induced changes in expression of long non-coding and coding RNAs in endothelial cells.Physiological reports · 2021Article
- The Role of Histone Protein Acetylation in Regulating Endothelial Function.Frontiers in cell and developmental biology · 2021Review
- Epigenetic Regulation of Angiogenesis in Development and Tumors Progression: Potential Implications for Cancer Treatment.Frontiers in cell and developmental biology · 2021Review
- Endothelial dysfunction in neuroprogressive disorders-causes and suggested treatments.BMC medicine · 2020Review
- BReast CAncer susceptibility gene 2 deficiency exacerbates oxidized LDL-induced DNA damage and endothelial apoptosis.Physiological reports · 2020Article
- Valproic Acid Decreases Endothelial Colony Forming Cells Differentiation and Induces Endothelial-to-Mesenchymal Transition-like Process.Stem cell reviews and reports · 2020Article
- Endothelial-specific Loss of IFT88 Promotes Endothelial-to-Mesenchymal Transition and Exacerbates Bleomycin-induced Pulmonary Fibrosis.Scientific reports · 2020Article
- Endothelial-to-Mesenchymal Transition in Cancer.Frontiers in cell and developmental biology · 2020Review
- Endothelial to Mesenchymal Transition: Role in Physiology and in the Pathogenesis of Human Diseases.Physiological reviews · 2019Review
- Endothelial-to-Mesenchymal Transition (EndoMT): Roles in Tumorigenesis, Metastatic Extravasation and Therapy Resistance.Journal of oncology · 2019Review
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, is a widely used anticonvulsant drug that is currently undergoing clinical evaluation for anticancer therapy due to its anti-angiogenic potential. Endothelial cells (ECs) can transition into mesenchymal cells and this form of EC plasticity is called endothelial-to-mesenchymal transition (EndMT), which is widely implicated in several pathologies including cancer and organ fibrosis. However, the effect of VPA on EC plasticity and EndMT remains completely unknown. We report herein that VPA-treatment significantly inhibits tube formation, migration, nitric oxide production, proliferation and migration in ECs. A microscopic evaluation revealed, and qPCR, immunofluorescence and immunoblotting data confirmed EndMT-like phenotypic switching as well as an increased expression of pro-fibrotic genes in VPA-treated ECs. Furthermore, our data confirmed important and regulatory role played by TGFβ-signaling in VPA-induced EndMT. Our qPCR array data performed for 84 endothelial genes further supported our findings and demonstrated 28 significantly and differentially regulated genes mainly implicated in angiogenesis, endothelial function, EndMT and fibrosis. We, for the first time report that VPA-treatment associated EndMT contributes to the VPA-associated loss of endothelial function. Our data also suggest that VPA based therapeutics may exacerbate endothelial dysfunction and EndMT-related phenotype in patients undergoing anticonvulsant or anticancer therapy, warranting further investigation.
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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.