ArticleDiabetes2016
Hydrogen Sulfide Induces Keap1 S-sulfhydration and Suppresses Diabetes-Accelerated Atherosclerosis via Nrf2 Activation.
Article in Diabetes, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05457881 (Short-Term Endogenous Hydrogen Sulfide Upregulation For Vein Graft Disease), which is not on this map. Cited by 196 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Short-Term Endogenous Hydrogen Sulfide Upregulation For Vein Graft Disease
Who cites it
196 citing papers in PubMed, 1 synthesis or guideline pooled it, 328 citations in OpenAlex.
- Recent Advances in Molecular Research on Hydrogen Sulfide (HInternational journal of molecular sciences · 2022Pooled it
- Short-Term Pre-Operative Protein Caloric Restriction in Elective Vascular Surgery Patients: A Randomized Clinical Trial.Nutrients · 2021Trial
- Harnessing gasotransmitters for orthopaedic infection therapy: Mechanisms and advanced delivery platforms.Bioactive materials · 2027Review
- Gut microbiota-derived metabolites as context-dependent modulators of Nrf2 signaling in inflammation-driven carcinogenesis.Gut microbes · 2026Review
- What do we know about redox status? A review in neonates of mothers with preeclampsia.Annals of medicine · 2026Review
- Bioorthogonal dual-channel imaging of NO and HChemical science · 2026Article
- Hydrogen Sulfide-Regulated NF-κB Signaling via Persulfidation: A Review.Biomolecules · 2026Review
- Hydrogen sulfide-mediated protein s-persulfidation: a regulatory mechanism in cardiovascular homeostasis.Molecular medicine (Cambridge, Mass.) · 2026Review
- Covalent Modification of Keap1 by the Key Metabolic Cofactor Coenzyme A Under Oxidative and Metabolic Stress.Antioxidants (Basel, Switzerland) · 2026Article
- Hepatic supersulfides attenuate acetaminophen-induced liver injury via enhanced detoxification and anti-inflammatory mechanisms.Redox biology · 2026Article
- The Role of Ferroptosis in Diabetes Pathogenesis: Therapeutic Implications of Hydrogen Sulfide and Its Reactive Metabolites.Antioxidants (Basel, Switzerland) · 2026Review
- S-sulfhydration: Novel insights into the antioxidant and antiinflammation in age-related diseases.Journal of advanced research · 2026Review
- Hydrogen sulfide generated by cystathionine gamma lyase inhibits lysyl oxidase and protects against calcific tendinopathy.Journal of orthopaedic translation · 2026Article
- The Chronic Elevated Consumption ofInternational journal of molecular sciences · 2026Article
- Pathophysiology of reactive oxygen species (ROS).Archives of toxicology · 2026Review
- Targeting the Gut in Sepsis: Therapeutic Potential of Medical Gases.Biomolecules · 2026Review
- Peptide-functionalized membrane camouflage for endogenous HNature communications · 2026Article
- Naturally Occurring HHandbook of experimental pharmacology · 2026Review
- Reactive sulfur species as emerging immunomodulators: mechanistic insights and therapeutic prospects.Frontiers in immunology · 2026Review
- Microneedle Mediated Gas Delivery for Rapid Separation, Enhanced Drug Penetration, and Combined Therapy.Pharmaceutics · 2025Review
136 more citing papers are in PubMed but not listed here.
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Authors and funding
18 authors at 8 institutions in 3 countries.
Funding
Abstract
Hydrogen sulfide (H2S) has been shown to have powerful antioxidative and anti-inflammatory properties that can regulate multiple cardiovascular functions. However, its precise role in diabetes-accelerated atherosclerosis remains unclear. We report here that H2S reduced aortic atherosclerotic plaque formation with reduction in superoxide (O2 (-)) generation and the adhesion molecules in streptozotocin (STZ)-induced LDLr(-/-) mice but not in LDLr(-/-)Nrf2(-/-) mice. In vitro, H2S inhibited foam cell formation, decreased O2 (-) generation, and increased nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation and consequently heme oxygenase 1 (HO-1) expression upregulation in high glucose (HG) plus oxidized LDL (ox-LDL)-treated primary peritoneal macrophages from wild-type but not Nrf2(-/-) mice. H2S also decreased O2 (-) and adhesion molecule levels and increased Nrf2 nuclear translocation and HO-1 expression, which were suppressed by Nrf2 knockdown in HG/ox-LDL-treated endothelial cells. H2S increased S-sulfhydration of Keap1, induced Nrf2 dissociation from Keap1, enhanced Nrf2 nuclear translocation, and inhibited O2 (-) generation, which were abrogated after Keap1 mutated at Cys151, but not Cys273, in endothelial cells. Collectively, H2S attenuates diabetes-accelerated atherosclerosis, which may be related to inhibition of oxidative stress via Keap1 sulfhydrylation at Cys151 to activate Nrf2 signaling. This may provide a novel therapeutic target to prevent atherosclerosis in the context of diabetes.
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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.