Short-term effect of low-dose colchicine on inflammatory biomarkers, lipids, blood count and renal function in chronic coronary artery disease and elevated high-sensitivity C-reactive protein

Fiolet, Aernoud T L; Silvis, Max J. M.; Opstal, Tjerk S J; Bax, Willem A.; Horst, F.A.L. van der; Mosterd, Arend; Kleijn, Dominique P.V. de; Cornel, Jan H.

doi:10.1371/journal.pone.0237665

Cited by 35 publications

(45 citation statements)

References 40 publications

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“…Cardiovascular benefits of canakinumab were largest among those who achieved lowest levels of hs-CRP and IL-6 [47,48]. We previously showed a reduction in hs-CRP and IL-6 following 30 days of colchicine treatment in patients with chronic coronary disease and hs-CRP above 2 mg/L [49]. In the current study, with no hs-CRP criteria on inclusion, we also observed a reduction in hs-CRP.…”

Section: Nlrp3 In Coronary Disease and The Effects Of Colchicine On Inflammatory Markerssupporting

confidence: 72%

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

et al. 2021

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Background and aims: Colchicine reduces the risk of cardiovascular events in patients with coronary disease. Colchicine has broad anti-inflammatory effects and part of the atheroprotective effects have been suggested to be the result of NLRP3 inflammasome inhibition. We studied the effect of colchicine on extracellular vesicle (EV) NLRP3 protein levels and inflammatory markers, high sensitivity-CRP (hs-CRP) and interleukin (IL)-6, in patients with chronic coronary disease. Methods: In vitro, the NLRP3 inflammasome was stimulated in PMA-differentiated-and undifferentiated THP-1 cells. In vivo, measurements were performed in serum obtained from 278 participants of the LoDoCo2 trial, one year after randomization to colchicine 0.5 mg once daily or placebo. EVs were isolated using precipitation. NLRP3 protein presence in EVs was confirmed using iodixanol density gradient centrifugation. Levels of NLRP3 protein, hs-CRP and IL-6 were measured using ELISA. Results: In vitro, NLRP3 inflammasome stimulation showed an increase of EV NLRP3 protein levels. EV NLRP3 protein levels were lower in patients treated with colchicine (median 1.38 ng/mL), compared to placebo (median 1.58 ng/mL) (p = 0.025). No difference was observed in serum NLRP3 protein levels. Serum hs-CRP levels were lower in patients treated with colchicine (median 0.80 mg/L) compared to placebo (median 1.34 mg/L) (p < 0.005). IL-6 levels were lower in patients treated with colchicine (median 2.07 ng/L) compared to placebo (median 2.59 ng/L), although this was not statistically significant (p = 0.076). Conclusions: Colchicine leads to a reduction of EV NLRP3 protein levels. This indicates that inhibitory effects on the NLRP3 inflammasome might contribute to the atheroprotective effects of colchicine in coronary disease.

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Section: Nlrp3 In Coronary Disease and The Effects Of Colchicine On Inflammatory Markerssupporting

confidence: 72%

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

et al. 2021

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“…For example, the LoDoCo2 trial 9 showed the efficacy of low-dose colchicine (also tested in the COLCOT trial 7 ) for the secondary prevention of cardiovascular events in patients with stable coronary artery disease. This effect was associated with a reduction in the circulating levels of hsCRP and of proteins involved in the activation of the NLRP3 inflammasome 10 , 11 . However, treatment with colchicine did not reduce the risk of cardiovascular death, and the incidences of death from any cause and non-cardiovascular death were higher in the colchicine-treated group than in the placebo group.…”

Section: Introductionmentioning

confidence: 99%

Immune cell profiling in atherosclerosis: role in research and precision medicine

Fernandez

Giannarelli

2021

Nat Rev Cardiol

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Inflammation is intimately involved at all stages of atherosclerosis and remains a substantial residual cardiovascular risk factor in optimally treated patients. The proof of concept that targeting inflammation reduces cardiovascular events in patients with a history of myocardial infarction has highlighted the urgent need to identify new immunotherapies to treat patients with atherosclerotic cardiovascular disease. Importantly, emerging data from new clinical trials show that successful immunotherapies for atherosclerosis need to be tailored to the specific immune alterations in distinct groups of patients. In this Review, we discuss how single-cell technologies -such as single-cell mass cytometry, single-cell RNA sequencing and cellular indexing of transcriptomes and epitopes by sequencing -are ideal for mapping the cellular and molecular composition of human atherosclerotic plaques and how these data can aid in the discovery of new precise immunotherapies. We also argue that single-cell data from studies in humans need to be rigorously validated in relevant experimental models, including rapidly emerging single-cell CRISPR screening technologies and mouse models of atherosclerosis. Finally, we discuss the importance of implementing single-cell immune monitoring tools in early phases of drug development to aid in the precise selection of the target patient population for data-driven translation into randomized clinical trials and the successful translation of new immunotherapies into the clinic.

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“…Colchicine is well known as an anti-inflammatory drug used in the treatment of acute gouty arthritis, familial Mediterranean fever and Behçet’s disease 1 . Additionally, it has been used for the treatment of pericarditis 2 , atrial fibrillation post-coronary bypass, stroke and for secondary prevention of cardiac events 3 – 7 . More recently it has been investigated in the setting of coronary artery disease (CAD) 8 – 11 .…”

Section: Introductionmentioning

confidence: 99%

Colchicine inhibits ROS generation in response to glycoprotein VI stimulation

Pennings

Reddel

Traini

et al. 2021

Sci Rep

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Colchicine inhibits coronary and cerebrovascular events in patients with coronary artery disease (CAD), and although known to have anti-inflammatory properties, its mechanisms of action are incompletely understood. In this study, we investigated the effects of colchicine on platelet activation with a particular focus on its effects on activation via the collagen glycoprotein (GP)VI receptor, P2Y12 receptor, and procoagulant platelet formation. Therapeutic concentrations of colchicine in vitro (equivalent to plasma levels) significantly decreased platelet aggregation in whole blood and in platelet rich plasma in response to collagen (multiplate aggregometry) and reduced reactive oxygen species (ROS) generation (H2DCF-DA, flow cytometry) in response to GPVI stimulation with collagen related peptide-XL (CRP-XL, GPVI specific agonist). Other platelet activation pathways including P-selectin expression, GPIIb/IIIa conformational change and procoagulant platelet formation (GSAO+/CD62P+) (flow cytometry) were inhibited with higher concentrations of colchicine known to inhibit microtubule depolymerization. Pathway specific mechanisms of action of colchicine on platelets, including modulation of the GPVI receptor pathway at low concentrations, may contribute to its protective role in CAD.

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Short-term effect of low-dose colchicine on inflammatory biomarkers, lipids, blood count and renal function in chronic coronary artery disease and elevated high-sensitivity C-reactive protein

Cited by 35 publications

References 40 publications

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

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

Immune cell profiling in atherosclerosis: role in research and precision medicine

Colchicine inhibits ROS generation in response to glycoprotein VI stimulation

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