Center for Metabolomics and Bioanalysis, Facultad de Farmacia, Universidad CEU San Pablo, Madrid, Spain.
PLoS One. 2012;7(2):e31982. doi: 10.1371/journal.pone.0031982. Epub 2012 Feb 24.
Abdominal aortic aneurysm (AAA) is a permanent and localized aortic dilation, defined as aortic diameter ≥3 cm. It is an asymptomatic but potentially fatal condition because progressive enlargement of the abdominal aorta is spontaneously evolving towards rupture.Biomarkers may help to explain pathological processes of AAA expansion, and allow us to find novel therapeutic strategies or to determine the efficiency of current therapies. Metabolomics seems to be a good approach to find biomarkers of AAA. In this study, plasma samples of patients with large AAA, small AAA, and controls were fingerprinted with LC-QTOF-MS. Statistical analysis was used to compare metabolic fingerprints and select metabolites that showed a significant change. Results presented here reveal that LC-QTOF-MS based fingerprinting of plasma from AAA patients is a very good technique to distinguish small AAA, large AAA, and controls. With the use of validated PLS-DA models it was possible to classify patients according to the disease stage and predict properly the stage of additional AAA patients. Identified metabolites indicate a role for sphingolipids, lysophospholipids, cholesterol metabolites, and acylcarnitines in the development and progression of AAA. Moreover, guanidinosuccinic acid, which mimics nitric oxide in terms of its vasodilatory action, was found as a strong marker of large AAA.
腹主动脉瘤(AAA)是一种永久性和局限性的主动脉扩张,定义为主动脉直径≥3cm。它是一种无症状但潜在致命的疾病,因为腹主动脉的进行性扩大是自发向破裂方向发展的。生物标志物可能有助于解释 AAA 扩张的病理过程,并使我们能够找到新的治疗策略或确定当前治疗方法的效果。代谢组学似乎是寻找 AAA 生物标志物的一个很好的方法。在这项研究中,使用 LC-QTOF-MS 对大 AAA、小 AAA 和对照组患者的血浆样本进行了指纹图谱分析。统计分析用于比较代谢指纹图谱并选择显示显著变化的代谢物。这里呈现的结果表明,基于 LC-QTOF-MS 的 AAA 患者血浆指纹图谱分析是区分小 AAA、大 AAA 和对照组的非常好的技术。使用经过验证的 PLS-DA 模型,可以根据疾病阶段对患者进行分类,并正确预测其他 AAA 患者的阶段。鉴定出的代谢物表明鞘脂、溶血磷脂、胆固醇代谢物和酰基辅酶 A 在 AAA 的发展和进展中起作用。此外,胍基琥珀酸被发现是大 AAA 的一个强标志物,其在血管扩张作用方面类似于一氧化氮。