Nitroglycerine limits infarct size through S-nitrosation of cyclophilin D: a novel mechanism for an old drug.

Cardiovascular Research
Sofia-Iris BibliIoanna Andreadou

Abstract

Nitroglycerine (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. Adult 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. Low-dose ...Continue Reading

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Citations

Oct 17, 2019·International Journal of Molecular Sciences·Ricardo O S SoaresOrlando Castro-E-Silva
May 10, 2020·Journal of Cellular and Molecular Medicine·Ioanna AndreadouFabio Di Lisa
Dec 12, 2019·Drug Development Research·Natalia V NaryzhnayaPeter R Oeltgen
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Apr 16, 2020·Free Radical Biology & Medicine·Doria BoulghobraCyril Reboul
Jul 19, 2021·Basic Research in Cardiology·Ioanna AndreadouRainer Schulz

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