Abstract
Objective: Patients affected by primary aldosteronism (PA) display an increased risk of cardiovascular events compared to essential hypertension (EH). Endothelial dysfunction favours initiation and progression of atherosclerosis and circulating extracellular vesicles (EVs), reflecting endothelial cell activity, could represent one of the mediators of endothelial dysfunction in these patients. The aim of this study was to characterize circulating EVs from patients diagnosed with PA and to explore their functional significance. Design and method: Serum EVs were isolated from 12 patients with PA and 12 with EH, matched by sex, age and blood pressure, and compared with 8 NT controls. EVs were characterized by nanoparticle tracking analysis (NTA), fluorescence-activated cell sorting (FACS) analysis and gene expression profiling. Results: At NTA, EVs concentration was 2.2 times higher in PA patients (P = 0.033) compared with EH and a significant correlation between EV number and serum aldosterone and potassium levels was identified. FACS analysis demonstrated patients with PA presented a higher absolute number of endothelial-derived EVs compared to both patients with EH and NT controls. Through EV mRNA profiling, 15 up-regulated and 4 down-regulated genes in PA patients compared to EH were identified; moreover, EDN1 was expressed only in patients with PA. Micro-array platform was validated by qRT-PCR on 4 genes (CASP1, EDN1, F2R, HMOX1) involved in apoptosis, inflammation and endothelial dysfunction. Following unilateral adrenalectomy, EVs number and expression of CASP1 and EDN1 significantly decreased in PA patients (P < 0.05). Additionally, the incubation with PA-derived EVs reduced angiogenesis and induced apoptosis in vitro. Conclusions: We characterized for the first time circulating EVs in patients with PA. EVs might not only represent a marker of endothelial dysfunction, but also contribute themselves to vascular dysfunction in PA patients.
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