Colchicine reduces extracellular vesicle NLRP3 inflammasome protein levels in chronic coronary disease: A LoDoCo2 biomarker substudy

Silvis, Max J. M.; Fiolet, Aernoud T L; Opstal, Tjerk S J; Dekker, Mirthe; Suquilanda, Daniel; Zivkovic, Minka; Duyvendak, Michiel; Timmers, Leo; Bax, Willem A.; Mosterd, Arend; Cornel, Jan H.; Kleijn, Dominique P. V. de

doi:10.1016/j.atherosclerosis.2021.08.005

Cited by 31 publications

(25 citation statements)

References 50 publications

(75 reference statements)

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“…Otani et al [ 142 ] showed that colchicine inhibits NLRP3 inflammasome activation through inhibiting the expression of protein of mature IL-1β and cleaved caspase-1. The recent study reported by Silvis et al [ 143 ] investigated the inhibitory action of colchicine on NLRP3. This study analyzed the serum from 278 patients from the LoDoCo2 trial and found that NLRP3 protein was present in extracellular vesicles (EV).…”

Section: Molecular and Biochemical Targets Of Colchicinementioning

confidence: 99%

Therapeutic potential of colchicine in cardiovascular medicine: a pharmacological review

Zhang

Qin

et al. 2022

Acta Pharmacol Sin

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Colchicine is an ancient herbal drug derived from Colchicum autumnale . It was first used to treat familial Mediterranean fever and gout. Based on its unique efficacy as an anti-inflammatory agent, colchicine has been used in the therapy of cardiovascular diseases including coronary artery disease, atherosclerosis, recurrent pericarditis, vascular restenosis, heart failure, and myocardial infarction. More recently, colchicine has also shown therapeutic efficacy in alleviating cardiovascular complications of COVID-19. COLCOT and LoDoCo2 are two milestone clinical trials that confirm the curative effect of long-term administration of colchicine in reducing the incidence of cardiovascular events in patients with coronary artery disease. There is growing interest in studying the anti-inflammatory mechanisms of colchicine. The anti-inflammatory action of colchicine is mediated mainly through inhibiting the assembly of microtubules. At the cellular level, colchicine inhibits the following: (1) endothelial cell dysfunction and inflammation; (2) smooth muscle cell proliferation and migration; (3) macrophage chemotaxis, migration, and adhesion; (4) platelet activation. At the molecular level, colchicine reduces proinflammatory cytokine release and inhibits NF-κB signaling and NLRP3 inflammasome activation. In this review, we summarize the current clinical trials with proven curative effect of colchicine in treating cardiovascular diseases. We also systematically discuss the mechanisms of colchicine action in cardiovascular therapeutics. Altogether, colchicine, a bioactive constituent from an ancient medicinal herb, exerts unique anti-inflammatory effects and prominent cardiovascular actions, and will charter a new page in cardiovascular medicine.

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Section: Molecular and Biochemical Targets Of Colchicinementioning

confidence: 99%

Therapeutic potential of colchicine in cardiovascular medicine: a pharmacological review

Zhang

Qin

et al. 2022

Acta Pharmacol Sin

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“…Liraglutide ameliorated pro-atherogenic eMV release in women with gestational diabetes, highlighting atheroprotective effects of liraglutide [ 309 ]. Importantly, the anti-inflammatory drug colchicine, which has demonstrated beneficial effects on MACE after MI [ 310 ] and in patients with chronic coronary disease [ 311 ], inhibits NLR family pyrin domain containing 3 (NLRP3) inflammasome and reduces EV-associated NLRP3 protein levels [ 312 ].…”

Section: Extracellular Vesicles As Diagnostic and Prognostic Biomarkersmentioning

confidence: 99%

Extracellular Vesicles as Drivers of Immunoinflammation in Atherothrombosis

Suades

Greco

Padró

et al. 2022

Cells

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Atherosclerotic cardiovascular disease is the leading cause of morbidity and mortality all over the world. Extracellular vesicles (EVs), small lipid-bilayer membrane vesicles released by most cellular types, exert pivotal and multifaceted roles in physiology and disease. Emerging evidence emphasizes the importance of EVs in intercellular communication processes with key effects on cell survival, endothelial homeostasis, inflammation, neoangiogenesis, and thrombosis. This review focuses on EVs as effective signaling molecules able to both derail vascular homeostasis and induce vascular dysfunction, inflammation, plaque progression, and thrombus formation as well as drive anti-inflammation, vascular repair, and atheroprotection. We provide a comprehensive and updated summary of the role of EVs in the development or regression of atherosclerotic lesions, highlighting the link between thrombosis and inflammation. Importantly, we also critically describe their potential clinical use as disease biomarkers or therapeutic agents in atherothrombosis.

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“…118 Colchicine was recently found to reduce levels of NLRP3 inflammasome in EV isolated from patients with coronary disease. 133…”

Section: Colchicine Effects On Platelets In Vivomentioning

confidence: 99%

“…118 Colchicine was recently found to reduce levels of NLRP3 inflammasome in EV isolated from patients with coronary disease. 133 However, no study has yet tested for changes in platelet-derived EV after treatment with colchicine.…”

Section: Colchicine Effects On Platelets In Vivomentioning

confidence: 99%

Colchicine as a Modulator of Platelet Function: A Systematic Review

Reddel

Pennings

Chen

et al. 2022

Semin Thromb Hemost

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The microtubule inhibitor and anti-inflammatory agent colchicine is used to treat a range of conditions involving inflammasome activation in monocytes and neutrophils, and is now known to prevent coronary and cerebrovascular events. In vitro studies dating back more than 50 years showed a direct effect of colchicine on platelets, but as little contemporary attention has been paid to this area, we have critically reviewed the effects of colchicine on diverse aspects of platelet biology in vitro and in vivo. In this systematic review we searched Embase, Medline, and PubMed for articles testing platelets after incubation with colchicine and/or reporting a clinical effect of colchicine treatment on platelet function, including only papers available in English and excluding reviews and conference abstracts. We identified 98 relevant articles and grouped their findings based on the type of study and platelet function test. In vitro, colchicine inhibits traditional platelet functions, including aggregation, clotting, degranulation, and platelet-derived extracellular vesicle formation, although many of these effects were reported at apparently supraphysiological concentrations. Physiological concentrations of colchicine inhibit collagen- and calcium ionophore-induced platelet aggregation and internal signaling. There have been limited studies of in vivo effects on platelets. The colchicine-platelet interaction has the potential to contribute to colchicine-mediated reduction in cardiovascular events, but there is a pressing need for high quality clinical research in this area.

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Colchicine reduces extracellular vesicle NLRP3 inflammasome protein levels in chronic coronary disease: A LoDoCo2 biomarker substudy

Cited by 31 publications

References 50 publications

Therapeutic potential of colchicine in cardiovascular medicine: a pharmacological review

Therapeutic potential of colchicine in cardiovascular medicine: a pharmacological review

Extracellular Vesicles as Drivers of Immunoinflammation in Atherothrombosis

Colchicine as a Modulator of Platelet Function: A Systematic Review

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