ArticleAmerican journal of physiology. Lung cellular and molecular physiology2016
Histone deacetylation contributes to low extracellular superoxide dismutase expression in human idiopathic pulmonary arterial hypertension.
Article in American journal of physiology. Lung cellular and molecular physiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 53 citations in OpenAlex.
- Extracellular Superoxide Dismutase in Acute Respiratory Distress Syndrome: Pathogenic Mechanisms and Therapeutic Implications.Antioxidants (Basel, Switzerland) · 2026Review
- Article
- Role of Histone Deacetylase and Inhibitors in Cardiovascular Diseases.Cell proliferation · 2025Review
- Vascular EC-SOD limits the accumulation, proinflammatory profibrotic reprogramming, and hyaluronan binding of interstitial macrophages in hypoxia.American journal of physiology. Lung cellular and molecular physiology · 2025Article
- Review
- Redistribution of SOD3 expression due to R213G polymorphism affects pulmonary interstitial macrophage reprogramming in response to hypoxia.Physiological genomics · 2024Article
- 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
- Citrate: a key signalling molecule and therapeutic target for bone remodeling disorder.Frontiers in endocrinology · 2024Review
- Targeting oxidative stress as a preventive and therapeutic approach for cardiovascular disease.Journal of translational medicine · 2023Review
- The role of HDAC3 and its inhibitors in regulation of oxidative stress and chronic diseases.Cell death discovery · 2023Review
- Integrating epigenetics and metabolomics to advance treatments for pulmonary arterial hypertension.Biochemical pharmacology · 2022Review
- Management of oxidative stress and inflammation in cardiovascular diseases: mechanisms and challenges.Environmental science and pollution research international · 2021Review
- Extracellular Superoxide Dismutase Regulates Early Vascular Hyaluronan Remodeling in Hypoxic Pulmonary Hypertension.Scientific reports · 2020Article
- Alteration of Extracellular Superoxide Dismutase in Idiopathic Pulmonary Arterial Hypertension.Frontiers in medicine · 2020Article
- Redox Biology of Peroxisome Proliferator-Activated Receptor-γ in Pulmonary Hypertension.Antioxidants & redox signaling · 2019Review
- The dynamic uptake and release of SOD3 from intracellular stores in macrophages modulates the inflammatory response.Redox biology · 2019Article
- Epigenetic Inheritance Underlying Pulmonary Arterial Hypertension.Arteriosclerosis, thrombosis, and vascular biology · 2019Review
- Effect of Oxidative Stress on the Estrogen-NOS-NO-KOxidative medicine and cellular longevity · 2019Review
- Insights on the epigenetic mechanisms underlying pulmonary arterial hypertension.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2018Review
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Authors and funding
12 authors at 5 institutions in 1 country.
Funding
Abstract
Epigenetic mechanisms, including DNA methylation and histone acetylation, regulate gene expression in idiopathic pulmonary arterial hypertension (IPAH). These mechanisms can modulate expression of extracellular superoxide dismutase (SOD3 or EC-SOD), a key vascular antioxidant enzyme, and loss of vascular SOD3 worsens outcomes in animal models of pulmonary arterial hypertension. We hypothesized that SOD3 gene expression is decreased in patients with IPAH due to aberrant DNA methylation and/or histone deacetylation. We used lung tissue and pulmonary artery smooth muscle cells (PASMC) from subjects with IPAH at transplantation and from failed donors (FD). Lung SOD3 mRNA expression and activity was decreased in IPAH vs. FD. In contrast, mitochondrial SOD (Mn-SOD or SOD2) protein expression was unchanged and intracellular SOD activity was unchanged. Using bisulfite sequencing in genomic lung or PASMC DNA, we found the methylation status of the SOD3 promoter was similar between FD and IPAH. Furthermore, treatment with 5-aza-2'-deoxycytidine did not increase PASMC SOD3 mRNA, suggesting DNA methylation was not responsible for PASMC SOD3 expression. Though total histone deacetylase (HDAC) activity, histone acetyltransferase (HAT) activity, acetylated histones, and acetylated SP1 were similar between IPAH and FD, treatment with two selective class I HDAC inhibitors increased SOD3 only in IPAH PASMC. Class I HDAC3 siRNA also increased SOD3 expression. Trichostatin A, a pan-HDAC inhibitor, decreased proliferation in IPAH, but not in FD PASMC. These data indicate that histone deacetylation, specifically via class I HDAC3, decreases SOD3 expression in PASMC and HDAC inhibitors may protect IPAH in part by increasing PASMC SOD3 expression.
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