ArticleCardiovascular research2019
Nitroglycerine limits infarct size through S-nitrosation of cyclophilin D: a novel mechanism for an old drug.
Article in Cardiovascular research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 43 citations in OpenAlex.
- Apolipoprotein E drives microglia activation in the development of autoimmune uveitis through up-regulation of peptidyl prolyl isomerase F.Science advances · 2026Article
- S-Nitrosylation in Cardiovascular Disorders: The State of the Art.Biomolecules · 2025Review
- Review
- Facilitating Nitrite-Derived S-Nitrosothiol Formation in the Upper Gastrointestinal Tract in the Therapy of Cardiovascular Diseases.Antioxidants (Basel, Switzerland) · 2024Review
- Health position paper and redox perspectives on reactive oxygen species as signals and targets of cardioprotection.Redox biology · 2023Review
- Mitochondria in endothelial cells angiogenesis and function: current understanding and future perspectives.Journal of translational medicine · 2023Review
- Small-Molecule Cyclophilin Inhibitors Potently Reduce Platelet Procoagulant Activity.International journal of molecular sciences · 2023Article
- Interaction of Cardiovascular Nonmodifiable Risk Factors, Comorbidities and Comedications With Ischemia/Reperfusion Injury and Cardioprotection by Pharmacological Treatments and Ischemic Conditioning.Pharmacological reviews · 2023Review
- Remodeling of Liver and Plasma Lipidomes in Mice Lacking Cyclophilin D.International journal of molecular sciences · 2022Article
- The Coadministration of Levosimendan and Exenatide Offers a Significant Cardioprotective Effect to Isolated Rat Hearts against Ischemia/Reperfusion Injury.Journal of cardiovascular development and disease · 2022Article
- A hypoxia-activated NO donor for the treatment of myocardial hypoxia injury.Chemical science · 2022Article
- Cyclophilin D: Guardian or Executioner for Tumor Cells?Frontiers in oncology · 2022Review
- Role of Nitric Oxide and Protein S-Nitrosylation in Ischemia-Reperfusion Injury.Antioxidants (Basel, Switzerland) · 2021Review
- Cysteine 202 of cyclophilin D is a site of multiple post-translational modifications and plays a role in cardioprotection.Cardiovascular research · 2021Article
- Targeting the pathways of regulated necrosis: a potential strategy for alleviation of cardio-cerebrovascular injury.Cellular and molecular life sciences : CMLS · 2021Review
- Mouse models of atherosclerosis and their suitability for the study of myocardial infarction.Basic research in cardiology · 2020Review
- Interplay of the red blood cell and vascular endothelial nitric oxide synthase system to combat cardiac complications of anemia.Basic research in cardiology · 2020Article
- The role of mitochondrial reactive oxygen species, NO and HJournal of cellular and molecular medicine · 2020Review
- Cyclophilin D: An Integrator of Mitochondrial Function.Frontiers in physiology · 2020Review
- Ischemia/Reperfusion Injury Revisited: An Overview of the Latest Pharmacological Strategies.International journal of molecular sciences · 2019Review
Corrections and comments
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Authors and funding
12 authors at 7 institutions in 5 countries.
Funding
Abstract
aimsNitroglycerine (NTG) given prior to an ischaemic insult exerts cardioprotective effects. However, whether administration of an acute low dose of NTG in a clinically relevant manner following an ischaemic episode limits infarct size, has not yet been explored. METHODS AND
resultsAdult mice were subjected to acute myocardial infarction in vivo and then treated with vehicle or low-dose NTG prior to reperfusion. This treatment regimen minimized myocardial infarct size without affecting haemodynamic parameters but the protective effect was absent in mice rendered tolerant to the drug. Mechanistically, NTG was shown to nitrosate and inhibit cyclophilin D (CypD), and NTG administration failed to limit infarct size in CypD knockout mice. Additional experiments revealed lack of the NTG protective effect following genetic (knockout mice) or pharmacological inhibition (L-NAME treatment) of the endothelial nitric oxide synthase (eNOS). The protective effect of NTG was attributed to preservation of the eNOS dimer. Moreover, NTG retained its cardioprotective effects in a model of endothelial dysfunction (ApoE knockout) by preserving CypD nitrosation. Human ischaemic heart biopsies revealed reduced eNOS activity and exhibited reduced CypD nitrosation.
conclusionLow-dose NTG given prior to reperfusion reduces myocardial infarct size by preserving eNOS function, and the subsequent eNOS-dependent S-nitrosation of CypD, inhibiting cardiomyocyte necrosis. This novel pharmacological action of NTG warrants confirmation in clinical studies, although our data in human biopsies provide promising preliminary results.
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