Department of Cardiothoracic Surgery, St George's Hospital University of London, London, UK.
Proteomics Clin Appl. 2013 Aug;7(7-8):504-15. doi: 10.1002/prca.201300016. Epub 2013 Jul 9.
Aortic aneurysm is a deceptively indolent disease that can cause severe complications such as aortic rupture and dissection. In the normal aorta, vascular smooth muscle cells within the medial layer produce and sustain the extracellular matrix (ECM) that provides structural support but also retains soluble growth factors and regulates their distribution. Although the ECM is an obvious target to identify molecular processes leading to structural failure within the vessel wall, an in-depth proteomics analysis of this important sub-proteome has not been performed. Most proteomics analyses of the vasculature to date used homogenized tissue devoid of spatial information. In such homogenates, quantitative proteomics comparisons are hampered by the heterogeneity of clinical samples (i.e. cellular composition) and the dynamic range limitations stemming from highly abundant cellular proteins. An unbiased proteomics discovery approach targeting the ECM instead of the cellular proteome may decipher the complex, multivalent signals that are presented to cells during aortic remodelling. A better understanding of the ECM in healthy and diseased vessels will provide important pathogenic insights and has potential to reveal novel biomarkers.
主动脉瘤是一种具有欺骗性的惰性疾病，可导致严重并发症，如主动脉破裂和夹层。在正常的主动脉中，中层的血管平滑肌细胞产生并维持细胞外基质 (ECM)，为血管壁提供结构支撑，同时保留可溶性生长因子并调节其分布。尽管 ECM 是确定导致血管壁结构破坏的分子过程的明显靶点，但对这一重要亚蛋白组的深入蛋白质组学分析尚未进行。迄今为止，对血管系统的大多数蛋白质组学分析都使用缺乏空间信息的均质化组织。在这种匀浆中，由于临床样本（即细胞组成）的异质性以及源于高丰度细胞蛋白的动态范围限制，定量蛋白质组学比较受到阻碍。针对 ECM 而不是细胞蛋白质组的无偏蛋白质组学发现方法可能会破译在主动脉重塑过程中呈现给细胞的复杂、多价信号。对健康和患病血管中 ECM 的更好理解将提供重要的发病机制见解，并有可能揭示新的生物标志物。
