Calprotectin is a contributor to and potential therapeutic target for vascular calcification in chronic kidney disease

钙蛋白酶 医学 肾脏疾病 钙化 内科学 透析 生物标志物 胃肠病学 内分泌学 疾病 生物 生物化学 炎症性肠病
作者
Ana Amaya-Garrido,Manon Brunet,Bénédicte Buffin‐Meyer,Alexis Piedrafita,Lucile Grzesiak,Ezechiel Agbegbo,Arnaud Del Bello,Inès Ferrandiz,Şerban Ardeleanu,Marcelino Bermúdez-López,C. Fédou,Mylène Camus,Odile Burlet‐Schiltz,Jean Massines,Marie Buléon,Guylène Feuillet,Mélinda Alvès,Eric Neau,Audrey Casemayou,Benjamin Breuil
出处
期刊:Science Translational Medicine [American Association for the Advancement of Science]
卷期号:15 (712) 被引量:24
标识
DOI:10.1126/scitranslmed.abn5939
摘要

Vascular calcification is an important risk factor for cardiovascular (CV) mortality in patients with chronic kidney disease (CKD). It is also a complex process involving osteochondrogenic differentiation of vascular smooth muscle cells (VSMCs) and abnormal deposition of minerals in the vascular wall. In an observational, multicenter European study, including 112 patients with CKD from Spain and 171 patients on dialysis from France, we used serum proteome analysis and further validation by ELISA to identify calprotectin, a circulating damage-associated molecular pattern protein, as being independently associated with CV outcome and mortality. This was confirmed in an additional cohort of 170 patients with CKD from Sweden, where increased serum calprotectin concentrations correlated with increased vascular calcification. In primary human VSMCs and mouse aortic rings, calprotectin exacerbated calcification. Treatment with paquinimod, a calprotectin inhibitor, as well as pharmacological inhibition of the receptor for advanced glycation end products and Toll-like receptor 4 inhibited the procalcifying effect of calprotectin. Paquinimod also ameliorated calcification induced by the sera of uremic patients in primary human VSMCs. Treatment with paquinimod prevented vascular calcification in mice with chronic renal failure induced by subtotal nephrectomy and in aged apolipoprotein E–deficient mice as well. These observations identified calprotectin as a key contributor of vascular calcification, and increased circulating calprotectin was strongly and independently associated with calcification, CV outcome, and mortality in patients with CKD. Inhibition of calprotectin might therefore be a promising strategy to prevent vascular calcification in patients with CKD.
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
CLY完成签到,获得积分10
刚刚
1秒前
rita_sun1969完成签到,获得积分10
2秒前
研友_8K2QJZ完成签到,获得积分10
2秒前
蝴蝶完成签到 ,获得积分10
3秒前
ARIA完成签到 ,获得积分10
3秒前
大橙子发布了新的文献求助10
6秒前
Bismarck完成签到,获得积分20
7秒前
7秒前
爱笑子默完成签到,获得积分10
8秒前
8秒前
一点完成签到,获得积分10
10秒前
研友_VZG7GZ应助大葱鸭采纳,获得10
10秒前
DezhaoWang完成签到,获得积分10
11秒前
知犯何逆发布了新的文献求助10
12秒前
原本完成签到,获得积分10
12秒前
Bismarck发布了新的文献求助10
13秒前
苗条丹南完成签到 ,获得积分10
15秒前
yu完成签到 ,获得积分10
18秒前
skyleon完成签到,获得积分10
18秒前
无心的天真完成签到 ,获得积分10
19秒前
Engen完成签到,获得积分20
19秒前
20秒前
学术小垃圾完成签到,获得积分10
20秒前
dreamwalk完成签到 ,获得积分10
20秒前
黄淮科研小白龙完成签到 ,获得积分10
21秒前
齐嫒琳完成签到,获得积分10
23秒前
研友_Lav0Qn完成签到,获得积分10
23秒前
大橙子发布了新的文献求助10
24秒前
GreenT完成签到,获得积分10
24秒前
鳄鱼队长完成签到,获得积分10
25秒前
Zengyuan完成签到,获得积分10
25秒前
研友_Lav0Qn发布了新的文献求助10
26秒前
perry4rosa完成签到,获得积分0
26秒前
量子星尘发布了新的文献求助10
27秒前
LIFE2020完成签到 ,获得积分10
27秒前
科研人完成签到,获得积分10
28秒前
飞云完成签到 ,获得积分10
29秒前
满天星辰独览完成签到 ,获得积分10
29秒前
九天完成签到 ,获得积分10
30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 4038157
求助须知:如何正确求助?哪些是违规求助? 3575869
关于积分的说明 11373842
捐赠科研通 3305650
什么是DOI,文献DOI怎么找? 1819255
邀请新用户注册赠送积分活动 892655
科研通“疑难数据库(出版商)”最低求助积分说明 815022