The fibrous cap: a promising target in the pharmacotherapy of atherosclerosis

Yanev, S.; Zhelyazkova-Savova, Maria; Chaldakov, George N.

doi:10.14748/bmr.v30.6394

Cited by 4 publications

(3 citation statements)

References 33 publications

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“…In these patients, colchicine administration is effective in the reduction of adverse CO. This may be explained by colchicine effects on inflammatory cytokines involved in atherosclerotic plaque growth and rupture [ 48 ], 49 .…”

Section: Discussionmentioning

confidence: 99%

Colchicine efficacy and safety for the treatment of cardiovascular diseases

et al. 2021

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The emerging role of colchicine in the treatment of cardiovascular diseases is a strong demand for a comprehensive understanding of its efficacy and safety. This meta-analysis and systematic review aimed to study the efficacy in the reduction of adverse cardiovascular outcomes (CO), and the risk of colchicine-related adverse events (CRAEs). Fourteen thousand and nine eighty three patients from 22 randomized controlled trials (RCTs) were included, 9 in patients with coronary artery disease—CAD, 9 in patients with pericarditis, 4 in patients with atrial fibrillation—AF or heart failure. Colchicine was efficacious in the reduction of adverse CO across different settings: pericardial diseases (reduced risk of recurrent pericarditis, 17.6% vs. 35%, RR 0.50, 95% CI 0.41–0.61), CAD (reduced risk of cardiac death, myocardial infarction, stroke,coronary revascularization or hospitalization, 6.1% vs. 8.5%, RR 0.73, 95% CI 0.64–0.83), AF (reduced risk of arrhythmia recurrence, 14.2% vs. 22.7%, RR 0.62, 95% CI 0.44–0.88). Colchicine was associated with increased risk of gastrointestinal CRAEs (11.2% vs. 8.8%, RR 1.87, 95% CI 1.41–2.47) and drug discontinuation (5.4% vs. 3.7%, RR 1.58, 95% CI 1.25–1.99). In both cases, the risk was proportional to the daily dose or duration of treatment, possibly due to early drug discontinuation or tolerance. Other CRAEs (muscle-related, liver,hematologic,cutaneous, infections) were not increased by colchicine, as long as all-cause death (2.2% vs. 1.9%, RR 1.11, 95% CI 0.79–1.54) or non-cardiovascular death (1.5% vs. 1%, RR 1.43, 95% CI 0.93–2.19). Colchicine is efficacious and safe for the treatment of cardiovascular diseases. The risk of gastrointestinal CRAEs and drug discontinuation is not significant if colchicine is used at lower doses (0.5 mg daily) or for longer periods of time (> 6 months). Supplementary Information The online version contains supplementary material available at 10.1007/s11739-021-02654-7.

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Section: Discussionmentioning

confidence: 99%

Colchicine efficacy and safety for the treatment of cardiovascular diseases

et al. 2021

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“…For instance, the progression of the atherosclerotic plaque is, at least in part, a consequence of non-resolved inflammation due to an imbalance between the inflammatory lipid mediators leukotriene B4 and prostaglandin E2 (say Yin) and the resolving lipid mediators resolvin D2 (RvD2), maresin 1 (MaR1) and resolvin E1 (RvE1) (say Yang). In a therapeutic context, repetitive RvD2 and MaR1 delivery may prevent atheroprogression via a decrease in lymphocytes and macrophages accumulation along with increased fibrous cap thickness (2,3). Among others, an example of such a dual functionality appears to be the one that includes matrix metalloproteinases (MMP), a disintegrin and metalloproteinases (ADAM) and ADAM with thrombospondin motifs (ADAMTS), together with the endogenous tissue inhibitors of metalloproteinases (TIMP).…”

Section: Binary Nature Of Cell Lifementioning

confidence: 99%

“…Herein, we focus on the potential role of (i) the transcription factors TCF21 and KLF-4 in SMC phenotypic modulation, (ii) the matrix protein secretion of SMC, and (iii) the activity of proteinases (MMP, ADAM, ADAMTS, furin, and the MMP inducer CD147) in the remodeling of the fibrous cap towards its stabilization, that is, as an anti-atherosclerotic action. It is an updated and enlarged version of our 2019 Dance Round (2).…”

Section: Binary Nature Of Cell Lifementioning

confidence: 99%

Phenotypic modulation of smooth muscle cells and matrix metalloproteinases as targets for atherosclerotic plaque stabilization

et al. 2020

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Atherosclerosis and its complications, erosion and rupture of the plaque fibrous cap, lead to myocardial infarction and stroke, the main causes of mortality worldwide. In this setting, arterial smooth muscle cells (SMC) of the innermost media undergo phenotypic changes, a switch towards a secretory phenotype engaged in matrix proteins production. In its nature, this is a protective action that forms of a new arterial layer, the fibrous cap covering the plaque thrombogenic lipid core. The risk of plaque rupture is inversely correlated with the presence of secretory state SMC and collagen fibrils within the fibrous cap. Thus, fibrous cap remodeling appears to be the main determinant of plaque vulnerability. Herein, we focus on the potential role of (i) the transcription factors TCF21 and KLF-4 in SMC phenotypic modulation, (ii) the matrix protein secretion of SMC, and (iii) the activity of proteinases (MMP, ADAM, ADAMTS, furin, and the MMP inducer CD147) in this critical process. We argue that focusing on these basic pathways could contribute to the knowledge of fibrous cap stability that might be translated into clinical medicine.

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