Colchicine Attenuates Inflammation Beyond the Inflammasome in Chronic Coronary Artery Disease

医学 秋水仙碱 炎症体 炎症 冠状动脉疾病 内科学 心脏病学
作者
Tjerk S.J. Opstal,Renate M. Hoogeveen,Aernoud T.L. Fiolet,Max J. M. Silvis,Salem H.K. The,Willem A. Bax,Dominique P.V. de Kleijn,Arend Mosterd,Erik S.G. Stroes,Jan H. Cornel
出处
期刊:Circulation [Lippincott Williams & Wilkins]
卷期号:142 (20): 1996-1998 被引量:109
标识
DOI:10.1161/circulationaha.120.050560
摘要

◼ inflammationEditorial, see p 1901 I nflammation has a crucial role in the progression of atherosclerosis.COLCOT (Colchicine Cardiovascular Outcome Trial) recently showed cardiovascular benefit of treatment with colchicine. 1 Colchicine is an established anti-inflammatory drug, which attenuates NLRP3 (nucleotide-binding oligomerization domain-, leucine-rich repeat-, and pyrin domain-containing protein 3) inflammasome-mediated crystal-induced inflammation present in gout attributable to uric acid crystals and in atherosclerosis attributable to cholesterol crystals. 2Colchicine may inhibit phagocytosis and neutrophil activity. 3The effect of colchicine in human atherosclerosis is unclear.We studied the anti-inflammatory potential of colchicine in patients with chronic coronary artery disease by comparing serum samples before and after 30 days of colchicine treatment using targeted proteomics.We conducted a prospective open-label study during the 30-day run-in period of the LoDoCo2 trial (Low-Dose Colchicine 2; URL: https://www.anzctr.org.au/;identifier: ACTRN12614000093684), including 174 patients with a history (>6 months) of acute coronary syndrome.The study was approved by the Medical Research Ethics Comittees United (MEC-U) at Nieuwegein, the Netherlands.All patients provided informed consent.Patients with highly elevated high-sensitivity C-reactive protein (>10 mg/L) were excluded.All patients underwent blood sampling at baseline and after 30 days of colchicine 0.5 mg once daily in addition to regular care.Targeted proteomic analysis included 184 proteins measured in serum with Cardiovascular II and III panels (Olink; Uppsala, Sweden).The primary outcome was percent change in median protein levels from baseline after 30 days of colchicine treatment.Biomarker levels were presented using normalized protein expression, an arbitrary unit.Correction for multiple comparisons was performed by the Benjamini-Hochberg method with a false discovery rate (FDR) of 5%.The data that support the findings of this study are available from the corresponding author on reasonable request.The 30-day treatment period with colchicine resulted in a significant median reduction in serum expression of 37 proteins (P FDR <0.05).Attenuation of the NLRP3 inflammasome pathway was supported by a reduction of interleukin (IL)-18 (-4.8%;P FDR =0.020), IL-1 receptor antagonist (-8.6%;P FDR =0.006), and IL-6 (-9.7%;P FDR =0.009).The NLRP3 inflammasome cleaves pro-IL-18 and pro-IL-1β into their active form, and attenuation of IL-1β is reflected by attenuated levels of IL-1 receptor antagonist and IL-6.These effects may be partially upstream of the NLRP3 inflammasome inhibition, as suggested by a 10.7% reduction of NF-κB (nuclear factor-κB) essential modulator (P FDR =0.008), an activator of NF-κB, which is necessary for NLRP3 inflammasome activation.Eleven proteins showed a large median reduction (>10%) after colchicine (Fig- ure).
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
新新完成签到,获得积分10
1秒前
搜集达人应助小超超采纳,获得10
1秒前
付2完成签到,获得积分20
2秒前
55完成签到,获得积分20
2秒前
共享精神应助wangyup采纳,获得10
2秒前
小雨发布了新的文献求助10
3秒前
栉风沐雨完成签到,获得积分10
3秒前
4秒前
魔幻凝云发布了新的文献求助40
5秒前
posh完成签到 ,获得积分10
6秒前
6秒前
6秒前
8秒前
魔幻慕梅完成签到,获得积分10
8秒前
科研通AI2S应助结实的半双采纳,获得10
9秒前
9秒前
ionicliquids发布了新的文献求助10
9秒前
烂漫薯片完成签到,获得积分10
9秒前
SciGPT应助Passerby采纳,获得10
11秒前
上上谦完成签到,获得积分10
11秒前
11秒前
一裤子灰完成签到,获得积分10
12秒前
魔幻芒果发布了新的文献求助10
12秒前
12秒前
忧郁紫翠完成签到,获得积分20
13秒前
14秒前
芒果味猕猴桃完成签到,获得积分10
14秒前
柳叶小弯刀完成签到,获得积分10
15秒前
15秒前
wangchaofk完成签到,获得积分10
15秒前
圆圆发布了新的文献求助10
17秒前
星辰大海应助科研通管家采纳,获得10
18秒前
田様应助科研通管家采纳,获得10
18秒前
响什么捏应助科研通管家采纳,获得10
18秒前
搜集达人应助内向的大白采纳,获得20
18秒前
18秒前
yznfly应助科研通管家采纳,获得150
18秒前
Jasper应助科研通管家采纳,获得10
18秒前
18秒前
18秒前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
Cognitive Neuroscience: The Biology of the Mind 1000
Technical Brochure TB 814: LPIT applications in HV gas insulated switchgear 1000
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
Picture Books with Same-sex Parented Families: Unintentional Censorship 500
Nucleophilic substitution in azasydnone-modified dinitroanisoles 500
不知道标题是什么 500
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3970048
求助须知:如何正确求助?哪些是违规求助? 3514739
关于积分的说明 11175783
捐赠科研通 3250115
什么是DOI,文献DOI怎么找? 1795198
邀请新用户注册赠送积分活动 875630
科研通“疑难数据库(出版商)”最低求助积分说明 804951