Clinical Biobank, Department of Medical Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
Department of Vascular Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
Int J Mol Sci. 2023 Jun 16;24(12):10253. doi: 10.3390/ijms241210253.
Abdominal aortic aneurysm (AAA) is hallmarked by irreversible dilation of the infrarenal aorta. Lipid deposition in the aortic wall and the potential importance of a lipid disorder in AAA etiology highlight the need to explore lipid variation during AAA development. This study aimed to systematically characterize the lipidomics associated with AAA size and progression. Plasma lipids from 106 subjects (36 non-AAA controls and 70 AAA patients) were comprehensively analyzed using untargeted lipidomics. An AAA animal model was established by embedding angiotensin-II pump in ApoE mice for four weeks and blood was collected at 0, 2 and 4 weeks for lipidomic analysis. Using a false-discovery rate (FDR) < 0.05, a group of lysophosphatidylcholines (lysoPCs) were specifically decreased in AAA patients and mice. LysoPCs were principally lower in the AAA patients with larger diameter (diameter > 50 mm) than those with a smaller size (30 mm < diameter < 50 mm), and levels of lysoPCs were also found to be decreased with modelling time and aneurysm formation in AAA mice. Correlation matrices between lipids and clinical characteristics identified that the positive correlation between lysoPCs and HDL-c was reduced and negative correlations between lysoPCs and CAD rate, lysoPCs and hsCRP were converted to positive correlations in AAA compared to control. Weakened positive correlations between plasma lysoPCs and circulating HDL-c in AAA suggested that HDL-lysoPCs may elicit instinctive physiological effects in AAA. This study provides evidence that reduced lysoPCs essentially underlie the pathogenesis of AAA and that lysoPCs are promising biomarkers for AAA development.
腹主动脉瘤(AAA)的特征是肾下主动脉的不可逆扩张。主动脉壁中的脂质沉积和脂质紊乱在 AAA 病因学中的潜在重要性突出表明需要在 AAA 发展过程中探索脂质变化。本研究旨在系统地描述与 AAA 大小和进展相关的脂质组学。使用非靶向脂质组学分析了来自 106 名受试者(36 名非 AAA 对照和 70 名 AAA 患者)的血浆脂质。通过在 ApoE 小鼠中嵌入血管紧张素-II 泵,建立 AAA 动物模型,在 0、2 和 4 周时收集血液进行脂质组学分析。使用错误发现率(FDR)<0.05,一组溶血磷脂酰胆碱(lysoPC)在 AAA 患者和小鼠中特异性降低。AAA 患者中 lysoPC 主要在直径较大(直径>50mm)的患者中低于直径较小(30mm<直径<50mm)的患者,并且在 AAA 小鼠中随着建模时间和动脉瘤形成,lysoPC 的水平也发现降低。脂质与临床特征之间的相关矩阵表明,在 AAA 中,lysoPC 与 HDL-c 之间的正相关减弱,而 lysoPC 与 CAD 率和 hsCRP 之间的负相关转化为正相关。与对照相比,AAA 中血浆 lysoPC 与循环 HDL-c 之间的弱正相关表明,HDL-lysoPC 可能在 AAA 中引起本能的生理效应。本研究提供的证据表明,减少的 lysoPC 本质上是 AAA 发病机制的基础,并且 lysoPC 是 AAA 发展的有前途的生物标志物。