Platelet Proteomics Group, Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), Universidade Santiago de Compostela, Instituto de Investigación Sanitaria de Santiago (IDIS), Santiago de Compostela, Spain.
Grupo de Endocrinología Molecular y Celular, Instituto de Investigación Sanitaria de Santiago (IDIS), Servicio de Endocrinología, Xerencia de Xestión Integrada de Santiago (XXS), Santiago de Compostela, Spain.
Proteomics. 2019 Jan;19(1-2):e1800248. doi: 10.1002/pmic.201800248. Epub 2018 Dec 27.
Plasma-derived extracellular vesicles (EVs) have been extensively described as putative biomarkers in different diseases. Interestingly, increased levels of EVs subpopulations are well known to associate with obesity. The goal of this study is to identify EVs-derived biomarkers in plasma from obese patients in order to predict the development of pathological events associated with obesity. Samples are obtained from 22 obese patients and their lean-matched controls are divided into two cohorts: one for a 2D fluorescence difference gel electrophoresis (2D-DIGE)-based study, and the other one for a label free LC-MS/MS-based approach. EVs are isolated following a serial ultracentrifugation protocol. Twenty-two and 23 differentially regulated features are detected from 2D-DIGE and label free LC-MS/MS, respectively; most of them involve in the coagulation and complement cascades. Remarkably, there is an upregulation of complement C4, complement C3, and fibrinogen in obese patients following both approaches, the latter two also validated by 2D-western-blotting in an independent cohort. These results correlate with a proinflammatory and prothrombotic state of those individuals. On the other hand, a downregulation of adiponectin leading to an increased risk of suffering cardiovascular diseases has been shown. The results suggest the relevance of plasma-derived-EVs proteins as a source of potential biomarkers for the development of atherothrombotic events in obesity.
血浆衍生的细胞外囊泡（EVs）已被广泛描述为不同疾病的潜在生物标志物。有趣的是，EVs 亚群水平的升高与肥胖密切相关。本研究的目的是鉴定肥胖患者血浆中的 EVs 衍生生物标志物，以预测与肥胖相关的病理事件的发生。从 22 名肥胖患者中获取样本，并将其与瘦匹配的对照者分为两组：一组用于基于 2D 荧光差异凝胶电泳（2D-DIGE）的研究，另一组用于基于无标记 LC-MS/MS 的方法。通过连续超速离心方案分离 EVs。从 2D-DIGE 和无标记 LC-MS/MS 分别检测到 22 个和 23 个差异调节特征；其中大多数涉及凝血和补体级联反应。值得注意的是，两种方法均显示肥胖患者的补体 C4、补体 C3 和纤维蛋白原上调，后者在独立队列中通过 2D- Western-blotting 进一步验证。这些结果与这些个体的促炎和促血栓状态相关。另一方面，已经表明脂联素的下调导致患心血管疾病的风险增加。结果表明，血浆衍生的 EVs 蛋白作为肥胖患者动脉粥样血栓事件发展的潜在生物标志物的来源具有相关性。
