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Sökning: onr:"swepub:oai:portal.research.lu.se:publications/bd1f652b-39e0-4fde-8efd-6b4692e9012e" > Therapeutic S100A8/...

  • Vlad, Mihaela LoredanaInstitute of Cellular Biology and Pathology “Nicolae Simionescu”, (författare)

Therapeutic S100A8/A9 inhibition reduces NADPH oxidase expression, reactive oxygen species production and NLRP3 inflammasome priming in the ischemic myocardium

  • Artikel/kapitelEngelska2025

Förlag, utgivningsår, omfång ...

  • Elsevier,2025

Nummerbeteckningar

  • LIBRIS-ID:oai:portal.research.lu.se:publications/bd1f652b-39e0-4fde-8efd-6b4692e9012e
  • oai:portal.research.lu.se:publications/bd1f652b-39e0-4fde-8efd-6b4692e9012eURI
  • https://doi.org/10.1016/j.ejphar.2025.177575DOI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

Ingår i deldatabas

Klassifikation

  • Ämneskategori:ref swepub-contenttype
  • Ämneskategori:art swepub-publicationtype

Anmärkningar

  • Oxidative stress and alterations in redox signalling have been implicated in the pathophysiology of myocardial infarction (MI). NADPH oxidase (Nox) is an important source of reactive oxygen species (ROS) in the infarcted myocardium. Alarmin S100A8/A9 amplifies acute myocardial inflammation in MI and has been shown to be a promising therapeutic target to improve cardiac function post-MI. We aimed to elucidate the underlying mechanisms linking S100A8/A9, oxidative stress and the inflammatory response in MI. MI was induced by permanent left coronary artery ligation in C57BL/6J mice, followed by treatment with the S100A8/A9 inhibitor ABR-238901 (30 mg/kg) or PBS for 3 days. The in-vivo experiments were complemented with mechanistic studies on cultured macrophages (Mac), important cellular effectors in MI. Compared to sham-operated animals, we detected significant increases in the Nox1, Nox2, Nox4 catalytic subunits at mRNA and protein levels, and NADPH-dependent ROS production in the left ventricle of MI mice. S100A8/A9 blockade prevented the up-regulation of Nox1/2/4 expression, reduced ROS formation, suppressed NF-kB activation and prevented NLRP3 inflammasome priming and activation, leading to reduced levels of active IL-1β. In-vitro, S100A8/A9 induced gene expression of Nox catalytic subtypes and NLRP3 in Mac in a TLR4-dependent and dose-dependent manner. These effects were counteracted by pharmacological inhibition of S100A8/9, TLR4, Nox1/4 and Nox2. In conclusion, we show that Nox upregulation and ROS formation triggered by S100A8/A9 contributes to NLRP3 inflammasome priming and increased IL-1β production in the infarcted myocardium. These mechanisms can be therapeutically targeted to prevent inflammatory and oxidant myocardial damage in acute MI.

Ämnesord och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Mares, Razvan GheorghitaGeorge Emil Palade University of Medicine, Pharmacy, Science, and Technology,University of Medicine and Pharmacy of Târgu Mureș (författare)
  • Jakobsson, GabrielEXODIAB: Excellence of Diabetes Research in Sweden,Cardiac Inflammation Research Group,Hjärtinflammationsforskningsgrupp(Swepub:lu)12b6fa23-af90-42a7-a901-a2439ef7768c (författare)
  • Manea, Simona AdrianaInstitute of Cellular Biology and Pathology “Nicolae Simionescu”, (författare)
  • Lazar, Alexandra GelaInstitute of Cellular Biology and Pathology “Nicolae Simionescu”, (författare)
  • Preda, Mihai BogdanInstitute of Cellular Biology and Pathology “Nicolae Simionescu”, (författare)
  • Popa, Mirel AdrianInstitute of Cellular Biology and Pathology “Nicolae Simionescu”, (författare)
  • Simionescu, MayaInstitute of Cellular Biology and Pathology “Nicolae Simionescu”, (författare)
  • Schiopu, AlexandruEXODIAB: Excellence of Diabetes Research in Sweden,Cardiac Inflammation Research Group,EpiHealth: Epidemiology for Health,Hjärtinflammationsforskningsgrupp,Institute of Cellular Biology and Pathology “Nicolae Simionescu”,Skåne University Hospital(Swepub:lu)16dfb43b-cfd7-4716-bc2c-77c9e688bf67 (författare)
  • Manea, AdrianInstitute of Cellular Biology and Pathology “Nicolae Simionescu”, (författare)
  • null (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:European Journal of Pharmacology: Elsevier9960014-2999

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