Specialized pro-resolving mediators in vascular inflammation and atherosclerotic cardiovascular disease

Nature Reviews Cardiology, Journal Year: 2024, Volume and Issue: 21(11), P. 808 - 823

Published: Jan. 12, 2024

Language: Английский

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Low-dose colchicine for atherosclerosis: long-term safety

European Heart Journal, Journal Year: 2024, Volume and Issue: 45(18), P. 1596 - 1601

Published: April 10, 2024

Abstract Low-dose colchicine (0.5 mg daily) is now FDA-approved for secondary prevention in patients with coronary disease and will be increasingly prescribed clinical practice. In this State-of-the-Art Review, data were collated from contemporary systemic reviews of case reports, drug registries, placebo-controlled trials that assessed specific issues safety related to the continuous use a range settings inform physicians, pharmacists, absolute risks low-dose colchicine, including among individuals taking statin therapy. Based upon these collective data, it concluded aside mild diarrhoea on initiation typically subsides vast majority within week therapy, well tolerated very safe. It does not affect renal, liver, or cognitive function, has no adverse effects bleeding, wound healing, fertility, pregnancy, increase cancer, serious infection, cause-specific mortality. When appropriately without significant renal hepatic impairment, reports myelosuppression, myotoxicity, drug–drug interactions are rare more frequent than placebo, Physicians, can reassured absence impairment used safely atherosclerosis purpose reducing cardiovascular risk.

Language: Английский

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Effect of Colchicine on Coronary Plaque Stability in Acute Coronary Syndrome as Assessed by Optical Coherence Tomography: The COLOCT Randomized Clinical Trial

Circulation, Journal Year: 2024, Volume and Issue: 150(13), P. 981 - 993

Published: Aug. 22, 2024

BACKGROUND: Colchicine has been approved to reduce cardiovascular risk in patients with coronary heart disease on the basis of its potential benefits demonstrated COLCOT (Colchicine Cardiovascular Outcomes Trial) and LoDoCo2 (Low-Dose 2) studies. Nevertheless, there are limited data available about specific impact colchicine plaques. METHODS: This was a prospective, single-center, randomized, double-blind clinical trial. From May 3, 2021, until August 31, 2022, total 128 acute syndrome aged 18 80 years lipid-rich plaque (lipid pool arc >90°) detected by optical coherence tomography were included. The subjects randomly assigned 1:1 ratio receive either (0.5 mg once daily) or placebo for 12 months. primary end point change minimal fibrous cap thickness from baseline 12-month follow-up. RESULTS: Among patients, 52 group completed study. mean age 58.0±9.8 years, 25.0% female. Compared placebo, therapy significantly increased (51.9 [95% CI, 32.8 71.0] μm versus 87.2 69.9 104.5] μm; difference, 34.2 9.7 58.6] P =0.006), reduced average lipid (–25.2° –30.6° –19.9°] –35.7° –40.5° –30.8°]; –10.5° –17.7° –3.4°]; =0.004), angular extension macrophages (–8.9° –13.3° –4.6°] –14.0° –18.0° –10.0°]; –6.0° –11.8° –0.2°]; =0.044), high-sensitivity C-reactive protein level (geometric ratio, 0.6 0.4 1.0] 0.3 0.2 0.5]; 0.5 1.0]; =0.046), interleukin-6 0.8 1.1] 0.7]; 0.9]; =0.025), myeloperoxidase 1.0 1.2] 0.7 =0.047). CONCLUSIONS: Our findings suggested that resulted favorable effects stabilization at syndrome. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04848857.

Language: Английский

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Pathogenic pathways and therapeutic targets of inflammation in heart diseases: A focus on Interleukin‐1

European Journal of Clinical Investigation, Journal Year: 2023, Volume and Issue: 54(2)

Published: Oct. 14, 2023

Abstract Background An exuberant and dysregulated inflammatory response contributes to the development progression of cardiovascular diseases (CVDs). Methods This narrative review includes original articles reviews published over past 20 years found through PubMed. The following search terms (or combination terms) were considered: “acute pericarditis,” “recurrent “myocarditis,” “cardiac sarcoidosis,” “atherosclerosis,” myocardial infarction,” “inflammation,” “NLRP3 inflammasome,” “Interleukin‐1” “treatment.” Results Recent evidence supports role inflammation across a wide spectrum CVDs including myocarditis, pericarditis, cardiomyopathies (i.e. cardiac sarcoidosis) as well atherosclerotic CVD heart failure. Interleukins (ILs) are signalling mediators response. NACHT, leucine‐rich repeat pyrin‐domain containing protein 3 (NLRP3) inflammasome play key in producing IL‐1β, prototypical pro‐inflammatory cytokine involved CVDs. Other cytokines (e.g. tumour necrosis factor) have been implicated sarcoidosis. As proof this, IL‐1 blockade has proven efficacious pericarditis chronic coronary syndrome. Conclusion Tailored strategies aiming at quenching emerged promising treat In this article, we summarize recent regarding broad We also novel targeted therapeutic strategies.

Language: Английский

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Inflammation in Heart Failure: Mechanisms and Therapeutic Strategies

Cardiovascular Innovations and Applications, Journal Year: 2025, Volume and Issue: 9(1)

Published: Jan. 1, 2025

Cardiovascular disease remains a leading cause of death and disability worldwide. Heart failure (HF) is the end stage various cardiovascular diseases. Despite recent advancements in understanding HF pathogenesis treatment, prognosis patients with poor. Inflammation key player development HF, its role has been extensively studied. associated elevated risk adverse prognosis. Targeting cardiac inflammation suggested as promising treatment strategy for HF. However, almost all clinical trials on anti-inflammatory have not indicated improved outcomes, some reported deterioration condition, possibly because limited specific The summary inflammatory mechanisms contributing to different types, current anti-inflammation therapies results could provide new perspectives targeting through effective therapeutic strategies.

Language: Английский

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Atherosclerosis in diabetes mellitus: novel mechanisms and mechanism-based therapeutic approaches

Nature Reviews Cardiology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 13, 2025

Language: Английский

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The Effect of Colchicine on Platelet Function Profiles in Patients with Stable Coronary Artery Disease: The ECLIPSE Pilot Study

Cardiology and Therapy, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 18, 2025

This prospective, single-arm pharmacodynamic study assessed the effect of colchicine (COLC) [Strides Pharma UK Ltd, Watford, Hertfordshire, England] 0.5 mg administered orally once daily for 14 days on platelet reactivity with respect to aspirin reaction units (ARUs) and P2Y12 (PRUs). Twenty-two patients stable coronary artery disease (CAD) dual antiplatelet therapy (DAPT) maintenance clopidogrel were recruited. Baseline function was evaluated VerifyNow™ ARU PRU assays (Werfen, Bedford, MA, USA) post-completion COLC days. In this study, median baseline score 463, post-COLC it 436, which not statistically significant (p = 0.485). The mean difference in scores −18.31 (95% confidence interval [CI] −74.34 37.71, p 0.504). At baseline, 27.3% had "aspirin resistance" or non-responders, compared 13.6% 0.423). 210, 199, also 0.581). −7.31 CI −31.1 16.5, 0.530). 50% "clopidogrel 45.5% 0.999). Two experienced mild gastrointestinal upset during trial without interruption COLC, there no serious adverse events treatment-emergent events. There differences ARUs PRUs CAD. pilot could be clinically informative DAPT. Further studies are required confirm these exploratory findings. ClinicalTrials.gov identifier, NCT06567678, prospectively registered 20/8/2024.

Language: Английский

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The Emerging Role of Colchicine to Inhibit NOD-Like Receptor Family, Pyrin Domain Containing 3 Inflammasome and Interleukin-1β Expression in In Vitro Models

Biomolecules, Journal Year: 2025, Volume and Issue: 15(3), P. 367 - 367

Published: March 3, 2025

While the beneficial effects of colchicine on inflammation and infarcted myocardium have been documented, its impact cardiac fibroblast activation in context myocardial infarction (MI) remains unknown. This study aimed to investigate effect regulation NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome Interleukin-1β (IL-1β) expression fibroblasts. 3T3 fibroblasts were exposed 600 μM CoCl2 for 24 h simulate hypoxia, with normoxic cells as controls. Colchicine (1 μM) was administered h. ASC-NLRP3 colocalization IL-1β evaluated using immunofluorescence flow cytometry, respectively. Data analyzed t-tests one-way ANOVA post hoc tests. Hypoxia treatment significantly induced apoptosis-associated speck-like protein a CARD (ASC)-NLRP3 (p < 0.05). hypoxic reduced colocalization, although this reduction not statistically significant. Additionally, inhibited colchicine-treated compared those treated placebo The findings indicate that inhibits NLRP3 by disrupting ASC NLRP3, thereby reducing CoCl2-treated cells.

Language: Английский

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Inflammation Resolution-Based Treatment of Atherosclerosis using Biomimetic Nanocarriers Loaded with Specialized Pro-Resolving Lipid Mediators

Materials Today Bio, Journal Year: 2025, Volume and Issue: unknown, P. 101733 - 101733

Published: April 1, 2025

Recent studies have shown that chronic inflammation in atherosclerotic (ATH) lesions is due to an inability resolve the inflammatory response. We evaluated therapeutic potential of specialized pro-resolving mediators (SPMs) incorporated into biomimetic lipid nanoemulsions covered with macrophage membranes (Bio-LN/SPMs) enhance their stability, targeting, and bioactivity resolving plaque inflammation. utilized both vitro vivo experimental models test this hypothesis. In vitro, we found Bio-LN/SPMs significantly reduced markers VCAM-1, MCP-1 TNF-α-activated endothelial smooth muscle cells, iNOS, NLRP3 LPS-activated macrophages. contrast, free SPMs exhibited a more modest effect. vivo, i.v. administration ApoE-deficient mice progressive developed after for 4 8 weeks high-fat diet, plasma triglycerides, improved renal function, decreased proteins associated complement activation (i.e. C4d, C5b-9, IL-6, MCP-1) greater extent than other treatment groups. also affected circulated monocyte subpopulations by increasing percentage anti-inflammatory Ly6Clow monocytes reducing pro-inflammatory Ly6Chigh monocytes. Additionally, they promoted transition macrophages plaques reparative M2 phenotype. They production TNF-α, IL-1β, IL-6 cytokines, along deposits aorta mice. These findings demonstrate efficacy compared unincorporated standard (LN/SPMs), emphasizing as novel approach treating atherosclerosis diseases.

Language: Английский

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Protruding Aortic Plaque and Coronary Plaque Vulnerability

Journal of the American Heart Association, Journal Year: 2024, Volume and Issue: 13(2)

Published: Jan. 9, 2024

Background Protruding aortic plaque is known to be associated with an increased risk for future cardiac and cerebrovascular events. However, the relationship between protruding coronary characteristics has not been systematically investigated. Methods Results A total of 615 patients who underwent computed tomography angiography, preintervention optical coherence imaging were included. Coronary compared evaluate vulnerability in on angiography. patients, 186 (30.2%) older had more comorbidities such as hypertension, chronic kidney disease, a prior myocardial infarction than those without. They also higher prevalence plaques vulnerable features thin‐cap fibroatheroma (85 [45.7%] versus 120 [28.0%], P <0.001), lipid‐rich (165 [88.7%] 346 [80.7%], =0.014), macrophages (147 [79.0%] 294 [68.5%], =0.008), layered (117 [62.9%] 213 [49.7%], =0.002), rupture (96 [51.6%] 111 [25.9%], <0.001). Patients experienced major adverse events, including all‐cause mortality, nonfatal acute syndromes, stroke (27 [14.7%] 21 [4.9%], <0.001; 8 [4.3%] 1 [0.2%], 5 [2.7%] 3 [0.7%], =0.030; 2 [0.5%], =0.013, respectively). Conclusions The current study demonstrates that have are at

Language: Английский

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