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酶基质金属蛋白酶2和9与动脉粥样硬化全球负担中调节性T细胞免疫之间的相互作用

Crosstalk Between Enzyme Matrix Metalloproteinases 2 and 9 and Regulatory T Cell Immunity in the Global Burden of Atherosclerosis.

作者信息

Lekic A, Brekalo Z, Kvesic A, Kovacevic M, Baricev-Novakovic Z, Sutic I, Bulog A, Sutic I, Pavisic V, Mrakovcic-Sutic I

机构信息

Department of Basic Medical Sciences, Faculty of Health Studies, University of Rijeka, Rijeka, Croatia.

Department of Surgery, University Hospital Mostar, Mostar, Bosnia and Herzegovina.

出版信息

Scand J Immunol. 2017 Jul;86(1):65-71. doi: 10.1111/sji.12563.

Abstract

Changes in immune and inflammatory responses may play a crucial role in the development and progression of atherosclerosis, as an autoimmune, chronic and progressive inflammatory disease. Immunological activity and vascular inflammation during atherosclerosis can be modulated by autoimmune responses against self-antigens, according to changeable risk factors (cholesterol, oxidized low-density lipoprotein (ox-LDL) in the vascular wall, fatty acids, etc.), and accompanied by accumulation of leucocytes and proinflammatory cytokines, which stimulate the transcription of matrix metalloproteinases (MMPs), whose concentration are increased in foam cell-rich regions. Regulatory T cells (Tregs) represent a unique subpopulation of T cells specialized in the regulation of immune response and in the suppression of proatherogenic T cells. The aim of our study was to examine the interactions between the concentration of enzyme matrix metalloproteinases 2 and 9 (MMP-2 and 9) in urine and the percentage of Tregs in peripheral blood of two groups of patients: with carotid artery stenosis (CAS), undergoing surgery and with mild atherosclerosis (A) from general practice. The method of enzyme immunoassay (ELISA) was used to determine enzyme MMP expression, and Tregs was examined by flow cytometric analysis. Our data have showed a large increase in the enzyme MMP-2 and 9 in the urine of CAS and A patients in comparison with healthy controls and indicated this method as an easy marker for the monitoring of the development of atherosclerosis. Simultaneously, the diminished number of Tregs in the same patients pointed the importance of these regulatory mechanisms in the etiopathogenesis of atherosclerosis and possible Tregs-mediated therapy.

摘要

免疫和炎症反应的变化可能在动脉粥样硬化的发生和发展中起关键作用,动脉粥样硬化是一种自身免疫性、慢性和进行性炎症性疾病。根据可变的危险因素(胆固醇、血管壁中的氧化低密度脂蛋白(ox-LDL)、脂肪酸等),动脉粥样硬化期间的免疫活性和血管炎症可由针对自身抗原的自身免疫反应调节,并伴有白细胞和促炎细胞因子的积累,这些细胞因子刺激基质金属蛋白酶(MMPs)的转录,其浓度在富含泡沫细胞的区域增加。调节性T细胞(Tregs)代表T细胞的一个独特亚群,专门负责调节免疫反应和抑制促动脉粥样硬化的T细胞。我们研究的目的是检测两组患者尿液中基质金属蛋白酶2和9(MMP-2和9)的浓度与外周血中Tregs百分比之间的相互作用:一组是接受手术的颈动脉狭窄(CAS)患者,另一组是来自普通诊所的轻度动脉粥样硬化(A)患者。采用酶联免疫吸附测定法(ELISA)测定酶MMP的表达,并通过流式细胞术分析检测Tregs。我们的数据显示,与健康对照相比,CAS和A患者尿液中的酶MMP-2和9大幅增加,并表明该方法是监测动脉粥样硬化发展的一个简便标志物。同时,同一患者中Tregs数量的减少表明了这些调节机制在动脉粥样硬化发病机制中的重要性以及可能的Tregs介导的治疗方法。

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