ArticleCirculation2012
Histone deacetylation inhibition in pulmonary hypertension: therapeutic potential of valproic acid and suberoylanilide hydroxamic acid.
Article in Circulation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 140 papers.
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Who cites it
140 citing papers in PubMed, 258 citations in OpenAlex.
- Article
- Histone Modifications in Cardiovascular Disease: Mechanisms and Therapeutic Opportunities.MedComm · 2026Review
- Pulmonary Arterial Hypertension: Reconfiguring the Vascular Landscape to Reverse Remodeling.Cells · 2026Article
- Article
- Sotatercept in Pulmonary Arterial Hypertension: Molecular Mechanisms, Clinical Evidence, and Emerging Role in Reverse Remodelling.International journal of molecular sciences · 2026Review
- Rewriting the vascular script: epigenetic modifiers as scribes of metabolic reprogramming in pulmonary hypertension.Journal of molecular medicine (Berlin, Germany) · 2025Review
- Histone deacetylase inhibitors sensitize glioblastoma models to temozolomide and reprogram immunosuppressive myeloid cells.Scientific reports · 2025Article
- Review
- Role of Protein Lysine Acetylation in the Pathogenesis and Treatment of Obesity and Metabolic Syndrome.Current obesity reports · 2025Review
- The role of lactate metabolism and lactylation in pulmonary arterial hypertension.Respiratory research · 2025Review
- Review
- Mechanisms and treatment of pulmonary arterial hypertension.Nature reviews. Cardiology · 2025Review
- Editorial: Exploring the role of epigenetic modifications in pulmonary vascular disease pathogenesis.Frontiers in medicine · 2025Article
- Precision Medicine for Pulmonary Vascular Disease: The Future Is Now (2023 Grover Conference Series).Pulmonary circulation · 2025Article
- Review
- Histone deacetylase 6 as a novel promising target to treat cardiovascular disease.Cancer innovation · 2024Review
- Review
- Future Perspectives of Pulmonary Arterial Hypertension: A Review of Novel Pipeline Treatments and Indications.Drugs in R&D · 2024Review
- Pulmonary hypertension.Nature reviews. Disease primers · 2024Review
- CS1, a controlled-release formulation of valproic acid, for the treatment of patients with pulmonary arterial hypertension: Rationale and design of a Phase 2 clinical trial.Pulmonary circulation · 2024Article
80 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
backgroundEpigenetic programming, dynamically regulated by histone acetylation, is a key mechanism regulating cell proliferation and survival. Little is known about the contribution of histone deacetylase (HDAC) activity to the development of pulmonary arterial hypertension, a condition characterized by profound structural remodeling of pulmonary arteries and arterioles. METHODS AND
resultsHDAC1 and HDAC5 protein levels were elevated in lungs from human idiopathic pulmonary arterial hypertension and in lungs and right ventricles from rats exposed to hypoxia. Immunohistochemistry localized increased expression to remodeled vessels in the lung. Both valproic acid, a class I HDAC inhibitor, and suberoylanilide hydroxamic acid (vorinostat), an inhibitor of class I, II, and IV HDACs, mitigated the development of and reduced established hypoxia-induced pulmonary hypertension in the rat. Both valproic acid and suberoylanilide hydroxamic acid inhibited the imprinted highly proliferative phenotype of fibroblasts and R-cells from pulmonary hypertensive bovine vessels and platelet-derived growth factor-stimulated growth of human vascular smooth muscle cells in culture. Exposure to valproic acid and suberoylanilide hydroxamic acid was associated with increased levels of p21 and FOXO3 and reduced expression of survivin. The significantly higher levels of expression of cKIT, monocyte chemoattractant protein-1, interleukin-6, stromal-derived factor-1, platelet-derived growth factor-b, and S100A4 in R-cells were downregulated by valproic acid and suberoylanilide hydroxamic acid treatment.
conclusionsIncreased HDAC activity contributes to the vascular pathology of pulmonary hypertension. The effectiveness of HDAC inhibitors, valproic acid, and suberoylanilide hydroxamic acid, in models of pulmonary arterial hypertension supports a therapeutic strategy based on HDAC inhibition in pulmonary arterial hypertension.
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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.