小剂量秋水仙碱对慢性冠心病患者中性粒细胞和单核细胞表型和功能的影响:双盲随机安慰剂对照交叉研究》。

IF 6.3 2区 医学 Q1 PHARMACOLOGY & PHARMACY Clinical Pharmacology & Therapeutics Pub Date : 2024-08-08 DOI:10.1002/cpt.3394
Helin Tercan, Amber van Broekhoven, Harsh Bahrar, Tjerk Opstal, Benjamin C. Cossins, Nils Rother, Laura Rodwell, Siroon Bekkering, Saloua El Messaoudi, Niels P. Riksen, Jan H. Cornel
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引用次数: 0

摘要

最近进行的具有里程碑意义的试验表明,秋水仙碱在减少冠状动脉疾病患者的主要心血管事件方面大有裨益。然而,人们对其确切的作用机制仍知之甚少。本研究旨在揭示秋水仙碱对单核细胞和中性粒细胞表型和功能的影响。在有心肌梗死病史的患者中开展了一项随机双盲安慰剂对照交叉干预研究。在中性粒细胞中,秋水仙碱治疗可减少体内外刺激时 CD62L 的表达和 NGAL 的释放,并增加 PMA 诱导的 ROS 的产生。秋水仙碱对单核细胞的影响仅限于减少中性和非典型单核细胞的 HLA-DR 表达。此外,在 RNA 表达水平上,秋水仙碱不影响单核细胞表型,但影响中性粒细胞的各种免疫调节基因。总之,我们的研究表明,秋水仙碱会影响中性粒细胞的功能,特别是通过减少中性粒细胞的募集、降低 NGAL 的浓度和改变各种具有免疫调节潜能的基因的表达,而对单核细胞的影响是有限的。
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The Effect of Low-Dose Colchicine on the Phenotype and Function of Neutrophils and Monocytes in Patients with Chronic Coronary Artery Disease: A Double-Blind Randomized Placebo-Controlled Cross-Over Study

Recent landmark trials showed that colchicine provides a substantial benefit in reducing major cardiovascular events in patients with coronary artery disease. Yet, its exact mechanism of action is still poorly understood. This study aimed to unravel the effect of colchicine on monocyte and neutrophil phenotype and function. A randomized double-blind placebo-controlled cross-over intervention study was executed in patients with a history of myocardial infarction. In neutrophils, colchicine treatment decreased CD62L expression and NGAL release upon ex vivo stimulation and increased PMA-induced ROS production. The effects of colchicine on monocytes were limited to a decrease in HLA-DR expression in the intermediate and nonclassical monocytes. Also, on the level of RNA expression, colchicine did not affect monocyte phenotype, while affecting various immunomodulating genes in neutrophils. Overall, our study suggests that treatment with colchicine affects neutrophil function, particularly by reducing neutrophil recruitment, lowering concentrations of NGAL, and changing the expression of various genes with immunomodulatory potential, whereas the effect on monocytes is limited.

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来源期刊
CiteScore
12.70
自引率
7.50%
发文量
290
审稿时长
2 months
期刊介绍: Clinical Pharmacology & Therapeutics (CPT) is the authoritative cross-disciplinary journal in experimental and clinical medicine devoted to publishing advances in the nature, action, efficacy, and evaluation of therapeutics. CPT welcomes original Articles in the emerging areas of translational, predictive and personalized medicine; new therapeutic modalities including gene and cell therapies; pharmacogenomics, proteomics and metabolomics; bioinformation and applied systems biology complementing areas of pharmacokinetics and pharmacodynamics, human investigation and clinical trials, pharmacovigilence, pharmacoepidemiology, pharmacometrics, and population pharmacology.
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