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

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...

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Bibliographic Details
Published in:Atherosclerosis Vol. 269; pp. 262 - 271
Main Authors: Martínez, Gonzalo J., Celermajer, David S., Patel, Sanjay
Format: Journal Article
Language:English
Published: Ireland Elsevier B.V 01.02.2018
Subjects:
Acute coronary syndrome
Animals
Anti-Inflammatory Agents - therapeutic use
Arteries - drug effects
Arteries - metabolism
Arteries - pathology
Atherosclerosis
Atherosclerosis - drug therapy
Atherosclerosis - metabolism
Atherosclerosis - pathology
Colchicine
Colchicine - therapeutic use
Cytokines - metabolism
Humans
Inflammasome
Inflammasomes - antagonists & inhibitors
Inflammasomes - metabolism
Inflammation
Inflammation - drug therapy
Inflammation - metabolism
Inflammation - pathology
Inflammation Mediators - metabolism
Macrophages - drug effects
Macrophages - metabolism
Monocytes - drug effects
Monocytes - metabolism
Myocardial infarction
Neutrophils - drug effects
Neutrophils - metabolism
NLR Family, Pyrin Domain-Containing 3 Protein - antagonists & inhibitors
NLR Family, Pyrin Domain-Containing 3 Protein - metabolism
Plaque, Atherosclerotic
Signal Transduction - drug effects
Myocardial infarction
Inflammation
Inflammasome
Colchicine
Acute coronary syndrome
Atherosclerosis
ISSN:0021-9150, 1879-1484, 1879-1484
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Summary: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. •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.
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ISSN:0021-9150
1879-1484
1879-1484
DOI:10.1016/j.atherosclerosis.2017.12.027