A Combination of Proteomic Approaches Identifies A Panel of Circulating Extracellular Vesicle Proteins Related to the Risk of Suffering Cardiovascular Disease in Obese Patients.

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 was to identify EVs-derived biomarkers in plasma from obese patients in order to predict the development of pathological events associated with obesity. Samples were obtained from 22 obese patients and their lean-matched controls which were divided into two cohorts: one for a 2D-DIGE-based study, and the other one for a label free LC-MS/MS-based approach. EVs were isolated following a serial ultracentrifugation protocol. We detected 22 and 23 differentially regulated features from 2D-DIGE and label free LC-MS/MS, respectively; most of them involved in the coagulation and complement cascades. Remarkably, there was an up-regulation 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 pro-inflammatory and prothrombotic state of those individuals. On the other hand, we showed a down-regulation of adiponectin leading to an increased risk of suffering cardiovascular diseases. Our results suggest the relevance of plasma-derived-EVs proteins as a source of potential biomarkers for the development of atherothrombotic events in obesity. This article is protected by copyright. All rights reserved.