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人类腹主动脉瘤中巨噬细胞的特征:转录组学、蛋白质组学和抗体蛋白质芯片研究。

Profile of macrophages in human abdominal aortic aneurysms: a transcriptomic, proteomic, and antibody protein array study.

机构信息

INSERM U744, Lille, France.

出版信息

J Proteome Res. 2010 Jul 2;9(7):3720-9. doi: 10.1021/pr100250s.

Abstract

Abdominal aortic aneurysms (AAA) are defined by an increased aortic diameter and characterized by impairment of the extracellular matrix, macrophages infiltration and decreased density of smooth muscle cells. Our aim is to identify the key molecules involved in the pathogenesis of AAAs. This study investigated transcriptomic and proteomic profiles of macrophages from AAA patients (>50 mm aortic diameter) (n = 24) and peripheral arterial occlusion (PAO) patients without AAA detected (n = 18), who both needed a surgery. An antibody protein microarray, generated by printing antibodies onto membranes against proteins selected from the transcriptomic and proteomic analysis, was performed to validate the proteins differentially expressed specifically in macrophages and plasma from the same patients. We found a restricted number of proteins differentially expressed between AAA and PAO patients: TIMP-3, ADAMTS5, and ADAMTS8 that differ significantly in plasma of AAA patients compared to PAO patients, as found in the macrophages. In contrast to plasma MMP-9, soluble glycoprotein V (sGPV) and plasmin-antiplasmin complex levels, plasma TIMP-3 levels were not correlated to AAA size but interestingly correlated to sGPV, a platelet activation marker. Combining transcriptomic and proteomic is a valid approach to identify diseases causing proteins and potential biomarkers.

摘要

腹主动脉瘤(AAA)的定义为主动脉直径增大,并伴有细胞外基质损伤、巨噬细胞浸润和平滑肌细胞密度降低。我们的目的是确定与 AAA 发病机制相关的关键分子。本研究对来自 AAA 患者(主动脉直径>50mm)(n=24)和未发现 AAA 的外周动脉闭塞(PAO)患者(n=18)的巨噬细胞进行了转录组和蛋白质组分析,这些患者均需要进行手术。通过将针对从转录组和蛋白质组分析中选择的蛋白质的抗体打印到膜上来制作抗体蛋白质微阵列,以验证在相同患者的巨噬细胞和血浆中特异性表达的差异蛋白。我们发现 AAA 和 PAO 患者之间差异表达的蛋白质数量有限:TIMP-3、ADAMTS5 和 ADAMTS8,与巨噬细胞中的情况一样,AAA 患者的血浆中存在明显差异。与 MMP-9、可溶性糖蛋白 V(sGPV)和纤溶酶-抗纤溶酶复合物水平不同,血浆 TIMP-3 水平与 AAA 大小无关,但与血小板活化标志物 sGPV 呈显著相关。结合转录组和蛋白质组学是识别致病蛋白和潜在生物标志物的有效方法。

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