ArticleRespiratory research2022
Disulfiram attenuates hypoxia-induced pulmonary hypertension by inhibiting GSDMD cleavage and pyroptosis in HPASMCs.
Article in Respiratory research, 2022. 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, 24 citations in OpenAlex.
- Pharmaceutical therapies for pyroptosis in lung injury.Inflammopharmacology · 2026Review
- Radiotherapy and cytokines: A systems view of immunotherapy and toxicity (Review).International journal of molecular medicine · 2026Review
- Development of a novel GAK solution for efficient hypothermic preservation of NK cell viability and anti-tumor function.Stem cell research & therapy · 2026Article
- Targeting gasdermin D-mediated pyroptosis: a precision anti-inflammatory strategy for acute and chronic lung diseases.Inflammopharmacology · 2026Review
- Disulfiram Protects Against Multiorgan Injuries and Cell Pyroptosis via Inhibiting GSDMD in Severe Acute Pancreatitis Mice.Journal of cellular and molecular medicine · 2025Article
- Gasdermin D aggravates a mouse model of radiation-induced liver disease by promoting chemokine secretion and neutrophil recruitment.Nature communications · 2025Article
- New insights into pulmonary arterial hypertension: interaction between PANoptosis and perivascular inflammatory responses.Apoptosis : an international journal on programmed cell death · 2025Review
- Regulated vascular smooth muscle cell death in vascular diseases.Cell proliferation · 2024Review
- Lactate dehydrogenase A (LDHA)-mediated lactate generation promotes pulmonary vascular remodeling in pulmonary hypertension.Journal of translational medicine · 2024Article
- Urolithin A Protects against Hypoxia-Induced Pulmonary Hypertension by Inhibiting Pulmonary Arterial Smooth Muscle Cell Pyroptosis via AMPK/NF-κB/NLRP3 Signaling.International journal of molecular sciences · 2024Article
- Accelerating Cellular Uptake with Unnatural Amino Acid for Inhibiting Immunosuppressive Cancer Cells.Chemistry (Weinheim an der Bergstrasse, Germany) · 2024Article
- The Mechanism of Pyroptosis and Its Application Prospect in Diabetic Wound Healing.Journal of inflammation research · 2024Review
- Chemical modulation of gasdermin D activity: Therapeutic implications and consequences.Seminars in immunology · 2023Review
- Pyroptosis in cardiovascular diseases: Pumping gasdermin on the fire.Seminars in immunology · 2023Review
- Molecular regulation and therapeutic implications of cell death in pulmonary hypertension.Cell death discovery · 2023Review
- Precise Orchestration of Gasdermins' Pore-Forming Function by Posttranslational Modifications in Health and Disease.International journal of biological sciences · 2023Review
- Epigenetic regulation of programmed cell death in hypoxia-induced pulmonary arterial hypertension.Frontiers in immunology · 2023Review
- Inflammation and immunity in the pathogenesis of hypoxic pulmonary hypertension.Frontiers in immunology · 2023Review
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Authors and funding
5 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPulmonary hypertension (PH) is characterized by progressive pulmonary arterial remodelling, associated with different severities of inflammation and altered immune processes. Disulfiram eliminates the formation of N-gasdermin D (GSDMD) plasma membrane pores to prevent pyroptosis. Pyroptosis is a form of lytic cell death characterized by inflammasome activation and proinflammatory cytokine release that acts in the development of PH. We sought to investigate whether disulfiram could alleviate hypoxia-induced PH by inhibiting pyroptosis.
methodsTo investigate whether disulfiram alleviates the progression of pulmonary hypertension, rodents were exposed to chronic hypoxia (10% oxygen, 4 weeks) to induce PH. The severity of PH was assessed by measuring right ventricular systolic pressure, mean pulmonary artery pressure, and the degree of right ventricular hypertrophy. Western blotting was used to measure proteins associated with the pyroptosis pathway, and ELISA was performed to measure the secretion of IL-18 and IL-1β, both of which are the primary methods for assessing pyroptosis.
resultsIL-18 and IL-1β concentrations were higher in patients with PH than in normal controls. Disulfiram suppressed the progression of PH in mice and rats through the alleviation of pulmonary arterial remodelling. Pyroptosis-related proteins and the inflammasome were activated in rodent models of PH. Disulfiram inhibited the processing of GSDMD into N-GSDMD and attenuated the secretion of IL-1β and IL18. In vivo experiments showed that disulfiram also inhibited lytic death in HPASMCs.
conclusionsDisulfiram treatment reduces PH progression through suppressing vascular remodelling by inhibiting GSDMD cleavage and pyroptosis. It might become a novel therapeutic option for the treatment of PH.
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