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
jiaolulu发布了新的文献求助10
2秒前
量子星尘发布了新的文献求助10
2秒前
真的不想干活了完成签到,获得积分10
2秒前
美丽的依琴完成签到,获得积分10
3秒前
Xin完成签到,获得积分10
9秒前
Aurora.H完成签到,获得积分10
12秒前
12秒前
FashionBoy应助科研通管家采纳,获得10
13秒前
打打应助科研通管家采纳,获得10
13秒前
Jasper应助科研通管家采纳,获得10
13秒前
Ava应助科研通管家采纳,获得10
13秒前
顾矜应助科研通管家采纳,获得10
13秒前
上官若男应助科研通管家采纳,获得10
13秒前
duckspy发布了新的文献求助10
15秒前
15秒前
15秒前
xiaowan完成签到,获得积分10
16秒前
Terry完成签到,获得积分10
17秒前
张张张哈哈哈完成签到,获得积分10
17秒前
Research完成签到 ,获得积分10
17秒前
称心采枫完成签到 ,获得积分0
18秒前
18秒前
新新新新新发顶刊完成签到 ,获得积分10
19秒前
L3完成签到,获得积分10
20秒前
我是科研小能手完成签到,获得积分10
20秒前
风中的小丸子完成签到,获得积分10
21秒前
21秒前
时尚俊驰发布了新的文献求助10
22秒前
22秒前
22秒前
Grin完成签到,获得积分10
23秒前
周周完成签到,获得积分20
23秒前
24秒前
liufan完成签到 ,获得积分10
26秒前
guitarist完成签到 ,获得积分10
26秒前
饮汽水完成签到,获得积分10
26秒前
26秒前
yoyo20012623完成签到,获得积分10
27秒前
伦语发布了新的文献求助10
27秒前
韵苑完成签到,获得积分10
29秒前
高分求助中
【提示信息,请勿应助】关于scihub 10000
Les Mantodea de Guyane: Insecta, Polyneoptera [The Mantids of French Guiana] 3000
徐淮辽南地区新元古代叠层石及生物地层 3000
The Mother of All Tableaux: Order, Equivalence, and Geometry in the Large-scale Structure of Optimality Theory 3000
Handbook of Industrial Diamonds.Vol2 1100
Global Eyelash Assessment scale (GEA) 1000
Picture Books with Same-sex Parented Families: Unintentional Censorship 550
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 4038201
求助须知:如何正确求助?哪些是违规求助? 3575940
关于积分的说明 11373987
捐赠科研通 3305747
什么是DOI,文献DOI怎么找? 1819274
邀请新用户注册赠送积分活动 892662
科研通“疑难数据库(出版商)”最低求助积分说明 815022