Therapeutic potential of colchicine in cardiovascular medicine: a pharmacological review

Zhang, Fan-shun; He, Qing-ze; Qin, Chong; Little, Peter J.; Weng, Jianping; Xu, Suowen

doi:10.1038/s41401-021-00835-w

Cited by 74 publications

(60 citation statements)

References 312 publications

(192 reference statements)

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“…At low doses, colchicine prevents growth of microtubules, while it supports microtubule depolymerization at high doses. Colchicine’s effect on tubulin disruption prevents the formation of the inflammasome which results in less secretion of pro-inflammatory cytokines and impaired neutrophil function ( 9 , 19 ). Given this background, colchicine was explored as a novel anti-inflammatory treatment strategy in patients with coronary artery disease (CAD).…”

Section: Discussionmentioning

confidence: 99%

Colchicine Impacts Leukocyte Trafficking in Atherosclerosis and Reduces Vascular Inflammation

et al. 2022

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BackgroundInflammation strongly contributes to atherosclerosis initiation and progression. Consequently, recent clinical trials pharmacologically targeted vascular inflammation to decrease the incidence of atherosclerosis-related complications. Colchicine, a microtubule inhibitor with anti-inflammatory properties, reduced cardiovascular events in patients with recent acute coronary syndrome and chronic coronary disease. However, the biological basis of these observations remains elusive. We sought to explore the mechanism by which colchicine beneficially alters the course of atherosclerosis.Methods and ResultsIn mice with early atherosclerosis (Apoe-/- mice on a high cholesterol diet for 8 weeks), we found that colchicine treatment (0.25 mg/kg bodyweight once daily over four weeks) reduced numbers of neutrophils, inflammatory monocytes and macrophages inside atherosclerotic aortas using flow cytometry and immunohistochemistry. Consequently, colchicine treatment resulted in a less inflammatory plaque composition and reduced plaque size. We next investigated how colchicine prevented plaque leukocyte expansion and found that colchicine treatment mitigated recruitment of blood neutrophils and inflammatory monocytes to plaques as revealed by adoptive transfer experiments. Causally, we found that colchicine reduced levels of both leukocyte adhesion molecules and receptors for leukocyte chemoattractants on blood neutrophils and monocytes. Further experiments showed that colchicine treatment reduced vascular inflammation also in post-myocardial infarction accelerated atherosclerosis through similar mechanisms as documented in early atherosclerosis. When we examined whether colchicine also decreased numbers of macrophages inside atherosclerotic plaques by impacting monocyte/macrophage transitioning or in-situ proliferation of macrophages, we report that colchicine treatment did not influence macrophage precursor differentiation or macrophage proliferation using cell culture experiments with bone marrow derived macrophages.ConclusionsOur data reveal that colchicine prevents expansion of plaque inflammatory leukocytes through lowering recruitment of blood myeloid cells to plaques. These data provide novel mechanistic clues on the beneficial effects of colchicine in the treatment of atherosclerosis and may inform future anti-inflammatory interventions in patients at risk.

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Section: Discussionmentioning

confidence: 99%

Colchicine Impacts Leukocyte Trafficking in Atherosclerosis and Reduces Vascular Inflammation

et al. 2022

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“…Moreover, Deftereos et al performed a randomized clinical trial of patients with coronavirus infection and observed that participants who received colchicine had significantly improved time to clinical deterioration with HD (48). These recent study reported the benefit of colchicine in the prevention of coronavirus-related heart injury (11,48,49).…”

Section: Discussionmentioning

confidence: 99%

Colchicine Is a Weapon for Managing the Heart Disease Among Interstitial Lung Disease With Viral Infection: Have We Found the Holy Grail?

Yeh

Hung

Lin

et al. 2022

Front. Cardiovasc. Med.

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BackgroundThis study investigated the effect of colchicine use on the risks of heart disease (HD), pericarditis, endocarditis, myocarditis, cardiomyopathy, cardiac arrhythmia, and cardiac failure in patients having interstitial lung disease (ILD) with virus infection (ILD cohort).MethodsWe retrospectively enrolled ILD cohort between 2000 and 2013 from the Longitudinal Health Insurance Database and divided them into colchicine users (n = 12,253) and colchicine non-users (n = 12,253) through propensity score matching. The event of interest was the diagnosis of HD. The incidence of HD was analyzed using multivariate Cox proportional hazards models between colchicine users and the comparison cohort after adjustment for age, sex, medication, comorbidities, and index date based on the time-dependent analysis.ResultsColchicine users had a significantly lower risk of HD (aHR = 0.87, 95% confidence interval (CI]) = 0.82–0.92) than did the colchicine non-user. For colchicine non-users as the reference, the aHR (95% CI) of the patients who received colchicine of 2–7, 8–30, 31–150, and > 150 days were 0.89 (0.81–0.98), 0.84 (0.76–0.94), 090 (0.80–0.99), and 0.83 (0.74–0.93), respectively; regardless of duration use, the lower risk of HD persisted in colchicine users. The cumulative incidence of HD in colchicine users was significantly lower than that in the colchicine non-users (log-rank p < 0.001).ConclusionThe addition of short-term or long-term colchicine to standard medical therapy may have benefits to prevent the HD among the ILD patients concurrent with a virus infection or comorbidities even in elderly patients.

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“…Colchicine, another anti-inflammatory drug, showed beneficial effects on cardiovascular outcomes in patients with stable ( Nidorf et al, 2020 ) and acute coronary disease ( Tardif et al, 2019 ). Colchicine, at the molecular level, inhibits NLRP3 inflammasome, in addition to the inhibition of nuclear factor kappa B ( Zhang et al, 2022 ).…”

Section: Inflammation and Recurrent Ischemic Eventsmentioning

confidence: 99%

Role of Inflammation in Cardiac Remodeling After Acute Myocardial Infarction

Fonseca

Izar

2022

Front. Physiol.

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Atherosclerosis is defined as an inflammatory disease. Low-grade inflammation is present in all phases of the cardiovascular continuum, since the establishment of cardiovascular risk factors and ischemic heart disease until cardiovascular events, such as myocardial infarction, heart failure and death. Not all inflammatory pathways are linked to cardiovascular outcomes, and thus, not all anti-inflammatory approaches decrease cardiovascular events. The most common cause of ventricular remodeling and heart failure is ischemic heart disease. Biomarkers such as high-sensitivity C-reactive protein can identify individuals at risk of major cardiovascular complications, but this biomarker has no causal effect on cardiovascular disease. On the other hand, interleukin 6 appears to be causally associated with cardiovascular disease. CANTOS was the first proof of concept study showing that anti-inflammatory therapy reduces major cardiovascular outcomes. Based on many anti-inflammatory trials, only therapies acting on the NLRP3 inflammasome, or interleukin 1beta, showed benefits on cardiovascular disease. Ventricular remodeling, particularly after myocardial infarction seems also influenced by the intensity of inflammatory responses, suggesting that anti-inflammatory therapies may reduce the residual cardiovascular risk. Inflammasome (NLRP3) activation, subtypes of lymphocytes, interleukin 6, and some inflammatory biomarkers, are associated with larger infarct size and impaired ventricular function after myocardial infarction. Cardiovascular risk factors commonly present in patients with myocardial infarction, and advanced age are associated with higher inflammatory activity.

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Therapeutic potential of colchicine in cardiovascular medicine: a pharmacological review

Cited by 74 publications

References 312 publications

Colchicine Impacts Leukocyte Trafficking in Atherosclerosis and Reduces Vascular Inflammation

Colchicine Impacts Leukocyte Trafficking in Atherosclerosis and Reduces Vascular Inflammation

Colchicine Is a Weapon for Managing the Heart Disease Among Interstitial Lung Disease With Viral Infection: Have We Found the Holy Grail?

Role of Inflammation in Cardiac Remodeling After Acute Myocardial Infarction

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