ArticleInternational journal of molecular sciences2021
The Short-Chain Fatty Acid Butyrate Attenuates Pulmonary Vascular Remodeling and Inflammation in Hypoxia-Induced Pulmonary Hypertension.
Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 2 of them syntheses that pooled it.
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Who cites it
61 citing papers in PubMed, 2 syntheses or guidelines pooled it, 80 citations in OpenAlex.
- Gut microbiota metabolites in the immunoregulation of enteritis: research progress.Frontiers in immunology · 2025Pooled it
- Genetically determined gut microbiota associates with pulmonary arterial hypertension: a Mendelian randomization study.BMC pulmonary medicine · 2024Pooled it
- Oral Butyrate Reduces Progression of Kidney Damage in an L-NAME-Induced Diabetic Kidney Disease Mouse Model.Diabetes, obesity & metabolism · 2026Article
- Review
- Review
- Short-Chain Fatty Acids in Heart Failure with Preserved Ejection Fraction: Pathophysiological Roles and Therapeutic Potential.International journal of molecular sciences · 2026Review
- Pulmonary Hypertension Molecular Switch: HIF Signaling Pathway.Pulmonary circulation · 2026Review
- Butyrate and Butyrate-Producing Bacteria in Cardiovascular-Kidney-Metabolic Syndrome.Antioxidants (Basel, Switzerland) · 2026Review
- Altitude-Associated Divergence of the Gut Microbiome in Endangered Forest Musk Deer: Evidence From Integrated Metagenomics, Metabolomics, and Culturomics.Evolutionary applications · 2026Article
- Targeting the Hippo pathway in pulmonary arterial hypertension: emerging pharmacological strategies.Journal of hypertension · 2026Review
- From nanotechnology to immunomodulation: emerging strategies targeting macrophages in high altitude pulmonary hypertension.Journal of nanobiotechnology · 2026Review
- The Importance of Liver-Lung Communication in Pulmonary Vascular Diseases.Comprehensive Physiology · 2026Review
- Reduction in microbiota-derived short-chain fatty acids contributes to the pathogenesis of pulmonary arterial hypertension.Respiratory research · 2026Article
- Microbial short chain fatty acids: Effective histone deacetylase inhibitors in immune regulation (Review).International journal of molecular medicine · 2026Review
- Tryptophan metabolism: a potential link between the gut microbiota and pulmonary vascular remodeling in pulmonary hypertension.Frontiers in cellular and infection microbiology · 2026Review
- Microtubule dynamics and post-translational modifications in cardiovascular diseases: mechanisms and therapeutic implications.Frontiers in cardiovascular medicine · 2026Review
- Alterations in gut microbiota and plasma metabolites in pulmonary arterial hypertension secondary to congenital left-to-right shunt heart disease: potential mechanisms and biomarkers.Frontiers in genetics · 2026Article
- Gut microbiota in acute lung injury/acute respiratory distress syndrome: mechanistic insights and therapeutic opportunities via the gut-lung axis.Frontiers in cellular and infection microbiology · 2026Review
- Role of Histone Deacetylase and Inhibitors in Cardiovascular Diseases.Cell proliferation · 2025Review
- Rewriting the vascular script: epigenetic modifiers as scribes of metabolic reprogramming in pulmonary hypertension.Journal of molecular medicine (Berlin, Germany) · 2025Review
1 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pulmonary hypertension (PH) is a progressive cardiovascular disorder in which local vascular inflammation leads to increased pulmonary vascular remodeling and ultimately to right heart failure. The HDAC inhibitor butyrate, a product of microbial fermentation, is protective in inflammatory intestinal diseases, but little is known regarding its effect on extraintestinal diseases, such as PH. In this study, we tested the hypothesis that butyrate is protective in a Sprague-Dawley (SD) rat model of hypoxic PH. Treatment with butyrate (220 mg/kg intake) prevented hypoxia-induced right ventricular hypertrophy (RVH), hypoxia-induced increases in right ventricular systolic pressure (RVSP), pulmonary vascular remodeling, and permeability. A reversal effect of butyrate (2200 mg/kg intake) was observed on elevated RVH. Butyrate treatment also increased the acetylation of histone H3, 25-34 kDa, and 34-50 kDa proteins in the total lung lysates of butyrate-treated animals. In addition, butyrate decreased hypoxia-induced accumulation of alveolar (mostly CD68+) and interstitial (CD68+ and CD163+) lung macrophages. Analysis of cytokine profiles in lung tissue lysates showed a hypoxia-induced upregulation of TIMP-1, CINC-1, and Fractalkine and downregulation of soluble ICAM (sICAM). The expression of Fractalkine and VEGFα, but not CINC-1, TIMP-1, and sICAM was downregulated by butyrate. In rat microvascular endothelial cells (RMVEC), butyrate (1 mM, 2 and 24 h) exhibited a protective effect against TNFα- and LPS-induced barrier disruption. Butyrate (1 mM, 24 h) also upregulated tight junctional proteins (occludin, cingulin, claudin-1) and increased the acetylation of histone H3 but not α-tubulin. These findings provide evidence of the protective effect of butyrate on hypoxic PH and suggest its potential use as a complementary treatment for PH and other cardiovascular diseases.
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Registered trials
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