CIRCULATING EXTRACELLULAR VESICLES INCREASE THE EXPRESSION OF RHOA IN NORMOTENSIVE SUBJECTS UNDERWENT DIETARY SODIUM MODULATION

Objective: Sodium status affects osmoregulation and fluid balance, and recent evidence suggests a role in immune system modulation, endothelial cell function, and development of cardiovascular disease. Increase dietary sodium has been linked with hypertension. Circulating extracellular vesicles EVs) have been involved in vascular inflammation and endothelial dysfunction and may mirror physio-pathological processes occurring after manipulation of dietary sodium. The aim of the present study was to characterize circulating extracellular vesicles and assess their functional role in subjects underwent dietary sodium modulation. Design and method: Fifty normotensive subjects underwent 7 days of sodium restricted diet and then 7 days of sodium load. Circulating EVs were isolated after each diet phase and profiled by a flow cytometry multiplex bead-based platform, assessing the expression of their surface antigens. Bioinformatics was applied to identify intracellular targets of EV markers up regulated after high sodium diet (HSD) as compared to sodium restricted diet. Human microvascular endothelial cells (HMEC) were used as in vitro model to assess EV functional effects. Results: EV-carried CD14, CD25 and CD40 (from immune system), CD29, CD42a and CD62P (involved in coagulation and platelets activation), and CD31 (endothelial marker) increased after HSD. Protein-protein interactor network analysis identify RhoA as target of circulating vesicles carrying the overexpressed antigens. After incubation of HMECs with patient-derived EVs after HSD, we confirmed an increased expression of active RhoA. Conclusions: The modulation of dietary sodium influences the expression of circulating EV surface antigens involved in vascular inflammation, platelet activation and endothelial dysfunction. EVs may be mediators of the effect of sodium load by interacting with endothelial cells, leading to the activation of RhoA, known as player in the development of salt-sensitive hypertension.