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通过代谢组学方法揭示的人动脉粥样硬化性动脉瘤分泌的代谢物。

Metabolites secreted by human atherothrombotic aneurysms revealed through a metabolomic approach.

机构信息

Centro de Excelencia en Metabolómica y Bioanálisis, Faculty of Pharmacy, University San Pablo-CEU, Campus Montepríncipe, Boadilla del Monte, 28668 Madrid, Spain.

出版信息

J Proteome Res. 2011 Mar 4;10(3):1374-82. doi: 10.1021/pr101138m. Epub 2011 Jan 31.

Abstract

Abdominal aortic aneurysm (AAA) is perma-nent and localized dilation of the abdominal aorta. Intraluminal thrombus (ILT) is involved in evolution and rupture of AAA. Complex biological processes associated with AAA include oxidative stress, proteolysis, neovascularization, aortic inflammation, cell death, and extracellular matrix breakdown. Biomarkers of growth and AAA rupture could give a more nuanced indication for surgery, unveil novel pathogenic pathways, and open possibilities for pharmacological inhibition of growth. Differential analysis of metabolites released by normal and pathological arteries in culture may help to find molecules that have a high probability of later being found in plasma and start signaling processes or be useful diagnostic/prognostic markers. We used a LC-QTOF-MS metabolomic approach to analyze metabolites released by human ILT (divided into luminal and abluminal layers), aneurysm wall (AW), and healthy wall (HW). Statistical analysis was used to compare luminal with abluminal ILT layer, ILT with AW, and AW with HW to select the metabolites exchanged between tissue and external medium. Identified compounds are related to inflammation and oxidative stress and indicate the possible role of fatty acid amides in AAA. Some metabolites (e.g., hippuric acid) had not been previously associated to aneurysm, others (fatty acid amides) have arisen, indicating a very promising line of research.

摘要

腹主动脉瘤(AAA)是腹主动脉的永久性和局限性扩张。腔内血栓(ILT)参与 AAA 的演变和破裂。与 AAA 相关的复杂生物学过程包括氧化应激、蛋白水解、新生血管形成、主动脉炎症、细胞死亡和细胞外基质降解。生长和 AAA 破裂的生物标志物可以更细致地指示手术,揭示新的致病途径,并为生长的药理学抑制开辟可能性。分析培养的正常和病理动脉释放的代谢物的差异,可能有助于找到在血浆中更有可能被发现并开始信号转导过程或成为有用的诊断/预后标志物的分子。我们使用 LC-QTOF-MS 代谢组学方法分析了人 ILT(分为管腔和外膜层)、动脉瘤壁(AW)和健康壁(HW)释放的代谢物。统计分析用于比较管腔与外膜 ILT 层、ILT 与 AW 以及 AW 与 HW 之间的代谢物交换,以选择在组织和外介质之间交换的代谢物。鉴定出的化合物与炎症和氧化应激有关,表明脂肪酸酰胺在 AAA 中的可能作用。一些代谢物(如马尿酸)以前与动脉瘤无关,而另一些代谢物(脂肪酸酰胺)则表明存在非常有前途的研究方向。

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