ArticleScientific reports2020
Isoform-specific characterization of class I histone deacetylases and their therapeutic modulation in pulmonary hypertension.
Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 40 citations in OpenAlex.
- Research Progress of Histone Deacetylase and Its Inhibitors in Endometriosis.Reproductive sciences (Thousand Oaks, Calif.) · 2026Review
- A circulating MicroRNA signature for the diagnosis of pulmonary arterial hypertension and functional characterization of candidate miR-3168.Scientific reports · 2026Article
- GLI1 Promotes Hypoxia Induced Pyroptosis of PASMCs and Aggravates Pulmonary Arterial Hypertension in Rats by Upregulating HDAC1 Expression.Cardiovascular toxicology · 2026Article
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- Role of Histone Deacetylase and Inhibitors in Cardiovascular Diseases.Cell proliferation · 2025Review
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- Macrophage-driven immunopathology in pulmonary arterial hypertension: from mechanisms to targeted therapies.Frontiers in immunology · 2025Review
- Exploring the Causal Link Between Autoimmune Diseases and Pulmonary Arterial Hypertension: A Bidirectional Mendelian Randomization Study.Global heart · 2025Article
- Article
- Review
- Review
- Review
- 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
- Traditional Therapeutics and Potential Epidrugs for CVD: Why Not Both?Life (Basel, Switzerland) · 2023Review
- Switch-Independent 3A: An Epigenetic Regulator in Cancer with New Implications for Pulmonary Arterial Hypertension.Biomedicines · 2023Review
- Unraveling the epigenetic landscape of pulmonary arterial hypertension: implications for personalized medicine development.Journal of translational medicine · 2023Review
- Article
- Pathological Role of HDAC8: Cancer and Beyond.Cells · 2022Review
- Integrating epigenetics and metabolomics to advance treatments for pulmonary arterial hypertension.Biochemical pharmacology · 2022Review
- Bioinformatic analysis of dysregulated circular RNAs in pediatric pulmonary hypertension linked congenital heart disease.Translational pediatrics · 2022Article
Corrections and comments
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Authors and funding
15 authors at 7 institutions in 2 countries.
Funding
Abstract
Pharmacological modulation of class I histone deacetylases (HDAC) has been evaluated as a therapeutic strategy for pulmonary hypertension (PH) in experimental models of PH. However, information of their expression, regulation and transcriptional targets in human PH and the therapeutic potential of isoform-selective enzyme modulation are lacking. Comprehensive analysis of expression and regulation of class I HDACs (HDAC1, HDAC2, HDAC3 and HDAC8) was performed in cardiopulmonary tissues and adventitial fibroblasts isolated from pulmonary arteries (PAAF) of idiopathic pulmonary arterial hypertension (IPAH) patients and healthy donors. Cellular functions and transcriptional targets of HDAC enzymes were investigated. Therapeutic effects of pan-HDAC (Vorinostat), class-selective (VPA) and isoform-selective (CAY10398, Romidepsin, PCI34051) HDAC inhibitors were evaluated ex vivo (IPAH-PAAF, IPAH-PASMC) and in vivo (rat chronic hypoxia-induced PH and zebrafish angiogenesis). Our screening identifies dysregulation of class I HDAC isoforms in IPAH. Particularly, HDAC1 and HDAC8 were consistently increased in IPAH-PAs and IPAH-PAAFs, whereas HDAC2 and HDAC8 showed predominant localization with ACTA2-expressing cells in extensively remodeled IPAH-PAs. Hypoxia not only significantly modulated protein levels of deacetylase (HDAC8), but also significantly caused dynamic changes in the global histone lysine acetylation levels (H3K4ac, H3K9/K14ac and H3K27ac). Importantly, isoform-specific RNA-interference revealed that HDAC isoforms regulate distinct subset of transcriptome in IPAH-PAAFs. Reduced transcript levels of KLF2 in IPAH-PAAFs was augmented by HDAC8 siRNA and HDAC inhibitors, which also attenuated IPAH-associated hyperproliferation and apoptosis-resistance ex vivo, and mitigated chronic hypoxia-induced established PH in vivo, at variable degree. Class I HDAC isoforms are significantly dysregulated in human PAH. Isoform-selective HDAC inhibition is a viable approach to circumvent off-target effects.
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