Correlations Between Clinical Variables and Gene-expression Profiles in Carotid Plaque Instability
Correlations Between Clinical Variables and Gene-expression Profiles in Carotid Plaque Instability
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DOI：
10.1016/j.ejvs.2011.05.023
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发表时间：
2011-12-01
影响因子：
5.7
通讯作者：
Hedin, U.
中科院分区：
文献类型：
--
作者：
Razuvaev, A.;Ekstrand, J.;Hedin, U.
目的：中风是致残的主要原因之一，通常是由不稳定的颈动脉斑块引起的栓塞引起的。这项研究的目的是验证人类颈动脉内膜切除术的生物库作为进一步探索斑块不稳定途径的平台。为此，我们研究了斑块不稳定的临床参数和先前显示与斑块不稳定或血管壁愈合过程相关的基因表达之间的关系。方法：使用106例颈动脉内膜切除术的临床信息和基因表达芯片数据。结果：基质金属蛋白酶-9和基质金属蛋白酶-7在斑块中的表达是正常动脉的100倍。一般来说，与炎症相关的基因(如RANKL和CD68)在有症状的斑块中过度表达，而在无症状的斑块中表达。从栓塞术后2周内接受手术的患者身上获得的斑块显示，参与血管壁愈合反应的基因(包括弹性蛋白和胶原蛋白)上调。他汀类药物治疗以及回声密度高的病变与更稳定的表型相关。结论：在这里，我们证明了基因表达谱反映了临床参数。我们的结果表明，微阵列技术和临床变量可用于未来识别斑块不稳定性的中心分子通路。(C)2011年欧洲血管外科学会。爱思唯尔有限公司出版。保留所有权利。
Objective: Strokes, a major cause of disability, are often caused by embolism from unstable carotid plaques. The aim of this study was to validate a biobank of human carotid endarterectomies as a platform for further exploration of pathways for plaque instability. For this purpose, we investigated the relationship between clinical parameters of plaque instability and expression of genes previously shown to be associated with either plaque instability or healing processes in the vessel wall.Methods: A database of clinical information and gene-expression microarray data from 106 carotid endarterectomies were used.Results: Expression of matrix metalloproteinase (MMP)-9 and MMP-7 was 100-fold higher in plaques than in normal artery. In general, genes associated with inflammation (such as RANKL and CD68) were overexpressed in symptomatic compared with asymptomatic plaques. Plaques obtained from patients undergoing surgery within 2 weeks after an embolic event showed up-regulation of genes involved in healing reactions in the vessel wall (including elastin and collagen). Statin treatment, as well as echodense lesions, were associated with a more stable phenotype.Conclusion: Here, we demonstrate that gene-expression profiles reflect clinical parameters. Our results suggest that microarray technology and clinical variables can be used for the future identification of central molecular pathways in plaque instability. (C) 2011 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.