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The NLRP3 inflammasome and the emerging role of colchicine to inhibit atherosclerosis-associated inflammation

  • Gonzalo J. Martínez
    Affiliations
    Division of Cardiovascular Diseases, Pontificia Universidad Católica, Santiago, Chile
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  • David S. Celermajer
    Affiliations
    Department of Cardiology, Royal Prince Alfred Hospital, Sydney Medical School, The University of Sydney, Heart Research Institute, Sydney, New South Wales, Australia
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  • Sanjay Patel
    Correspondence
    Corresponding author. Department of Cardiology, Royal Prince Alfred Hospital, Missenden Rd, Camperdown, Sydney, NSW 2050, Australia.
    Affiliations
    Department of Cardiology, Royal Prince Alfred Hospital, Sydney Medical School, The University of Sydney, Heart Research Institute, Sydney, New South Wales, Australia
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      Highlights

      • The NLRP3 inflammasome leads to IL-1β (and IL-18) production.
      • IL-1β promotes atherosclerotic plaque development and destabilization.
      • Colchicine can block the NLRP3 inflammasome and thus IL-1β production.
      • Data suggest a favourable effect of colchicine on atherosclerosis-associated inflammation.
      • On going trials seek to clarify the role of colchicine in patients with atherosclerosis.

      Abstract

      Atherosclerosis is considered a chronic inflammatory disease of the arterial wall. Recently, compelling evidence has arisen for the role of monocytes and neutrophils and a particular protein complex that resides within these cells – the NLRP3 inflammasome – in atherosclerosis-associated inflammation. It is now also known that cholesterol crystals are present through all stages of atherosclerosis and can activate the NLRP3 inflammasome within these inflammatory cells to produce interleukin 1β and interleukin 18 – key mediators in the inflammatory cascade that drive plaque progression and instability.
      In this review, we describe the role of monocytes/macrophages and neutrophils in atherosclerosis, outline mechanisms of activation of the NLRP3 inflammasome in the setting of atherosclerosis-associated inflammation and discuss potential therapies that specifically target the NLRP3 inflammasome and/or its downstream mediators in atherosclerosis, with a particular focus on the emerging role of colchicine.

      Keywords

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      Linked Article

      • Corrigendum to: “The NLRP3 inflammasome and the emerging role of colchicine to inhibit atherosclerosis-associated inflammation” [Atherosclerosis. 2018 Feb;269:262–271]
        AtherosclerosisVol. 273
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          Page 5: In the fourth paragraph, the following text appears: “These data are supported by the favourable clinical effect of colchicine in patients with FMF, a disease associated with abnormal activation of the inflammasome secondary to mutations in MEFV, the gene that codes for the NLRP3 receptor.” This should read: “These data are supported by the favourable clinical effect of colchicine in patients with FMF, a disease associated with abnormal activation of the inflammasome secondary to mutations in MEFV, the gene that codes for Pyrin”.
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      • Inhibitory effects of colchicine on inflammasomes
        AtherosclerosisVol. 273
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          We read with great interest the review article “The NLRP3 inflammasome and the emerging role of colchicine to inhibit atherosclerosis-associated inflammation” by Martinez and colleagues, published in Atherosclerosis [1]. The review provides an up to date summary of the current understanding of atherosclerosis development and progression, with a special focus on the contributing inflammatory processes. We agree with the authors that cardiovascular diseases (CVDs) represent a major health burden in Western societies and that targeting the inflammatory components of CVDs holds promising therapeutic potential.
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      • Reply to: “Inhibitory effects of colchicine on inflammasomes”
        AtherosclerosisVol. 273
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          We thank Drs. Hoss and Latz for their letter [1] providing insights into inflammasome biology and suggesting some clarifications to our recently published review [2]. We agree that the study of inflammatory pathways is a promising field in atherosclerotic-related disease. Three major issues have been raised by the authors and will be addressed here.
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