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. 2025 Oct 23.
doi: 10.1161/HYPERTENSIONAHA.125.25101. Online ahead of print.

Effects of Dietary Sodium Modulation on Circulating Extracellular Vesicles

Jacopo Burrello  1 , Fabrizio Buffolo  1 , Brooke Honzel  2 , Laura Tsai  2 , Martina Tetti  1 , Alessio Burrello  3 , Dario Di Silvestre  4 , Pierluigi Mauri  4 , Virginia Capuzzo  1 , Stefania Bruno  5 , Lucio Barile  6 , Paolo Mulatero  1 , Anand Vaidya #  2 , Silvia Monticone #  1
Affiliations

Effects of Dietary Sodium Modulation on Circulating Extracellular Vesicles

Jacopo Burrello et al. Hypertension. .

Abstract

Background: Sodium is involved in osmoregulation, fluid balance, and immune system function. High sodium (HS) consumption is linked to endothelial dysfunction, hypertension, and mortality. Extracellular vesicles (EVs), nano-sized particles reflecting cellular status, could link dietary sodium to vascular and immune changes. This study aimed to characterize circulating EVs and assess their functional role on endothelial cells after dietary sodium modulation.

Methods: Fifty subjects underwent 2 dietary sodium interventions, each lasting 5 to 7 days: sodium-restriction (10-40 mmol/d, 0.23-0.92 g/d) followed by sodium-loading (intake above 180 mmol/d, 4.14 g/d). Serum EVs were isolated after each phase and analyzed using a flow cytometry bead-based platform. Bioinformatics identified intracellular targets of EV surface antigens upregulated after the HS diet. Human microvascular endothelial cells were used to assess EV effects in vitro.

Results: In matched comparison, after HS-diet, EVs exhibited increased levels of CD14-CD25-CD40 (immune system markers), CD29-CD42-CD62P (coagulation and platelets activation markers), and CD31 (endothelial marker). Among targets identified by signaling network analysis, the incubation of human microvascular endothelial cells with patient-derived EVs after HS-diet resulted in decreased expression of AKT1, increased expression of MAPK3, and levels of active RhoA. It also resulted in increased expression of ICAM1, the number of ICAM-1 positive human microvascular endothelial cells, and nitric oxide levels.

Conclusions: Dietary sodium modulates the expression of EV surface antigens associated with vascular inflammation, platelet activation, and endothelial function. Circulating EVs may mediate the effects of HS condition by interacting with endothelial cells, through multiple pathways, including RhoA activation and increased ICAM-1 expression.

Keywords: endothelium; extracellular vesicles; hypertension; inflammation; sodium.

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