CARDIOVASCULAR RISK STRATIFICATION IN YOUNG POPULATION: APPLICATION OF THIOL REDOX PROTEOMICS. (June 2018) - Alonso, N. Corbacho
Abstract : Objective: Cardiovascular (CV) diseases are the leading cause of death in developed countries and present high prevalence in developing countries. Nevertheless, there are no biomarkers available to detect the causal physiopathological process of the clinical illness, implying a high socioeconomic impact. Nowadays, CV risk estimators focus on age as the most important risk factor in CV events and mortality. The current study is focused on CV risk stratification attending to oxidative stress for the discovery of new markers for early detection of the physiopathological process. Design and method: 24 blood samples from a cohort of patients in average age of life (30–50 years old) classified in 3 groups of study according to their CV risk (healthy controls, patients with CV risk factors and patients with reported CV event in the last 3 years) were analyzed using FASILOX, a novel strategy for analysis of the dynamic thiol redox proteome. To our knowledge, this study constitutes the first description of reversible Cys oxidation in human plasma according to CV risk stratification. Results: We identified that reversible oxidations are decreased in CV events individuals compared with healthy subjects. Only proteins involved in coagulation cascade have reversible oxidations increased in CV events, biologic function directly linked with CV pathology, whose alteration could result in a CV event.We have also showed down-regulation of proteins involved in antioxidant respond, which is in line with the loss of redox homeostasis in CV events. Conclusions: CV events present a severe oxidative stress, exceeding antioxidant mechanisms as reversible oxidations of Cys, generating irreversible oxidations that together with the down-regulation of redoxins, generate an increase of molecular damage.The present draft of redox targets together with the quantification of protein and oxidative changes may help to better