B和T淋巴细胞衰减器可能是与慢性肾脏疾病相关的加速动脉粥样硬化的一个新参与者。

IF 6.7 2区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
Nuria Dolade, Sandra Rayego-Mateos, Alicia Garcia-Carrasco, Maryse Guerin, Jose-Luis Martín-Ventura, Marta Ruiz-Ortega, Pierre-Louis Tharaux, Jose Manuel Valdivielso
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引用次数: 0

摘要

背景:在慢性肾脏疾病(CKD)中,心血管疾病的死亡率高于普通人群。CKD加速了动脉粥样硬化性心血管疾病,但具体的CKD相关动脉粥样硬化危险因素尚不清楚。方法:采用来自NEFRONA研究的CKD患者。我们从基线时没有动脉粥样硬化斑块的患者的血液中进行了mRNA阵列,2年后有(n=10)和没有(n=10。选定的候选信使核糖核酸在更大的样本中得到验证(n=148)。在CKD加速动脉粥样硬化的实验模型中对经验证的候选者进行了体内研究,并在小鼠巨噬细胞中进行了体外研究。结果:mRNA阵列分析显示,在患有新发斑块的CKD患者的样本中,有92个mRNA上调,67个mRNA下调。功能分析指出了免疫反应的重要作用。在更大样本中的验证证实,B和T淋巴细胞共抑制分子(BTLA)下调与2年后新出现的斑块有关。然而,在基线时已有斑块的患者中,未发现BTLA下调与动脉粥样硬化进展有关。在CKD加速动脉粥样硬化模型中,血液样本和动脉粥样硬化斑块中BTLA的mRNA和蛋白表达水平显著降低。CKD动物的斑块比对照动物的斑块更大,炎症细胞浸润更多,IL6和IL17表达更高,胶原存在更少。巨噬细胞与大鼠尿毒症血清的孵育降低了BTLA的表达。结论:BTLA可能是CKD患者动脉粥样硬化发病率的潜在生物标志物或治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
B- and T-lymphocyte attenuator could be a new player in accelerated atherosclerosis associated with chronic kidney disease.

Background: In chronic kidney disease (CKD), cardiovascular morbi-mortality is higher than in general population. Atherosclerotic cardiovascular disease is accelerated in CKD, but specific CKD-related risk factors for atherosclerosis are unknown.

Methods: CKD patients from the NEFRONA study were used. We performed mRNA array from blood of patients free from atheroma plaque at baseline, with (n=10) and without (n=10) de novo atherosclerotic plaque development 2 years later. Selected mRNA candidates were validated in a bigger sample (n=148). Validated candidates were investigated in vivo in an experimental model of CKD-accelerated atherosclerosis, and in vitro in murine macrophages.

Results: mRNA array analysis showed 92 up-regulated and 67 down-regulated mRNAs in samples from CKD patients with de novo plaque development. The functional analysis pointed to a paramount role of the immune response. The validation in a bigger sample confirmed that B- and T-lymphocyte co-inhibitory molecule (BTLA) down-regulation was associated with de novo plaque presence after 2 years. However, BTLA down-regulation was not found to be associated with atherosclerotic progression in patients with plaque already present at baseline. In a model of CKD-accelerated atherosclerosis, mRNA and protein expression levels of BTLA were significantly decreased in blood samples and atheroma plaques. Plaques from animals with CKD were bigger, had more infiltration of inflammatory cells, higher expression of IL6 and IL17 and less presence of collagen than plaques from control animals. Incubation of macrophages with rat uremic serum decreased BTLA expression.

Conclusions: BTLA could be a potential biomarker or therapeutic target for atherosclerosis incidence in CKD patients.

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来源期刊
Clinical science
Clinical science 医学-医学:研究与实验
CiteScore
11.40
自引率
0.00%
发文量
189
审稿时长
4-8 weeks
期刊介绍: Translating molecular bioscience and experimental research into medical insights, Clinical Science offers multi-disciplinary coverage and clinical perspectives to advance human health. Its international Editorial Board is charged with selecting peer-reviewed original papers of the highest scientific merit covering the broad spectrum of biomedical specialities including, although not exclusively: Cardiovascular system Cerebrovascular system Gastrointestinal tract and liver Genomic medicine Infection and immunity Inflammation Oncology Metabolism Endocrinology and nutrition Nephrology Circulation Respiratory system Vascular biology Molecular pathology.
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