Abstract 012: Diagnosis Of Salt Sensitivity Of Blood Pressure Using Circulating Monocyte Isolevuglandin-CXCL/CCL Signaling In Response To Elevated Sodium In Vitro

Abstract

Salt sensitivity of blood pressure (SSBP) is when blood pressure changes parallel to salt loading/ depletion and is an independent risk factor for cardiovascular disease. Despite its importance, there is no feasible diagnosis, which limits investigational studies to identify therapeutic targets. Our studies indicate that changes in production of isolevuglandins (IsoLGs) in antigen presenting cells (APCs) parallel changes in blood pressure following salt-loading and depletion in humans and this is associated with chemokine signaling. We hypothesized that in vivo responses to salt-loading/depletion leading to IsoLG production in APCs are mirrored in vitro . To test this hypothesis, we isolated peripheral blood mononuclear cells from known salt-sensitive and salt-resistant people and treated them with either normal salt (140 mmoL) or high salt (190 mmoL) for 24 hours in vitro . Using flow cytometry, we found that classical monocytes from salt sensitive but not salt resistant people had a significant increase in IsoLGs (25.15 ± 7.41 vs 14.52 ± 8.60, p = 0.0022) after 24 hours of high salt treatment. To determine mechanisms, we also performed bulk RNAseq on in vitro high salt treated monocytes and CITEseq on PBMCs following the salt-loading/depletion protocol. We found that salt-loading/depletion was associated with parallel changes in the expression of various chemokines in the CXCL and CC families both in vitro and in vivo . Specifically, the changes in levels of CXCL8 (p = 0.01553, r = 0.8067) , CXCL16 (p = 0.004697, r = -0.8725), and CCL2 (p = 0.002292, r = -0.9004) correlated with changes in diastolic and systolic blood pressure from salt loading to depletion. Moreover, changes in systolic blood pressure significantly correlated with changes in CCL2 (p= 0.008878, r= -0.6302) and CCL4 (p= 0.03209, r = -0.5367) from salt loading to salt depletion. These data suggest that in vitro responses of IsoLGs and chemokine production to salt treatment could serve as a feasible diagnosis for salt sensitivity of blood pressure in the clinic.