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动脉粥样硬化斑块的分子特征:一组与蛋白相关的更新标记物。

Molecular signatures of atherosclerotic plaques: An up-dated panel of protein related markers.

机构信息

Biomedicine, Biotechnology and Public Health Department, Cadiz University, Spain; Institute of Biomedical Research Cadiz (INIBICA), Spain.

Institute of Biomedical Research Cadiz (INIBICA), Spain.

出版信息

J Proteomics. 2020 Jun 15;221:103757. doi: 10.1016/j.jprot.2020.103757. Epub 2020 Apr 1.

Abstract

Atherosclerosis remains the leading cause of ischemic syndromes such as myocardial infarction or brain stroke, mainly promoted by plaque rupture and subsequent arterial blockade. Identification of vulnerable or high-risk plaques constitutes a major challenge, being necessary to identify patients at risk of occlusive events in order to provide them with appropriate therapies. Clinical imaging tools have allowed the identification of certain structural indicators of prone-rupture plaques, including a necrotic lipidic core, intimal and adventitial inflammation, extracellular matrix dysregulation, and smooth muscle cell depletion and micro-calcification. Additionally, alternative approaches focused on identifying molecular biomarkers of atherosclerosis have also been applied. Among them, proteomics has provided numerous protein markers currently investigated in clinical practice. In this regard, it is quite uncertain that a single molecule can describe plaque rupture, due to the complexity of the process itself. Therefore, it should be more accurate to consider a set of markers to define plaques at risk. Herein, we propose a selection of 76 proteins, from classical inflammatory to recently related markers, all of them identified in at least two proteomic studies analyzing unstable atherosclerotic plaques. Such panel could be used as a prognostic signature of plaque instability.

摘要

动脉粥样硬化仍然是缺血性综合征(如心肌梗死或脑卒中等)的主要原因,主要由斑块破裂和随后的动脉阻塞引起。识别易损或高危斑块是一个主要的挑战,需要识别有闭塞事件风险的患者,以便为他们提供适当的治疗。临床影像学工具已经可以识别出易破裂斑块的某些结构指标,包括坏死的脂质核心、内膜和外膜炎症、细胞外基质失调、平滑肌细胞耗竭和微钙化。此外,还应用了一些关注识别动脉粥样硬化分子生物标志物的替代方法。其中,蛋白质组学提供了许多目前在临床实践中研究的蛋白质标志物。在这方面,由于该过程本身的复杂性,很难确定单一分子可以描述斑块破裂。因此,更准确的做法应该是考虑一组标志物来定义具有风险的斑块。在此,我们提出了 76 种蛋白质的选择,包括经典的炎症标志物和最近相关的标志物,这些标志物都是在至少两项分析不稳定动脉粥样硬化斑块的蛋白质组学研究中确定的。这样的标志物组合可以作为斑块不稳定的预后指标。

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