Abstract P109: Antigen Presenting Cell Activator Protein 1 Mediates Salt-sensitive Hypertension In Humans

Abstract

Salt-sensitivity of blood pressure (SSBP) is defined by the changes in blood pressure according to dietary sodium loading/depletion and is a major independent risk factor for morbidity and mortality due to cardiovascular disease, even in normotensive individuals. We previously found that SSBP is associated with activation of antigen presenting cells (APCs), but the underlying mechanisms are unknown. The activator protein 1 (AP-1) (Fos/Jun) has been implicated in mediating inflammation but its role in SSBP is not known. We hypothesized that AP-1 in APCs senses elevated sodium and contributes to SSBP. Using bulk RNA-sequencing in human monocytes, we found elevated sodium increases expression of the AP-1 gene family when compared to normal sodium concentration, including FOS (2378.18 ± 480.7 vs 6494.09 ± 945.55, p= 0.0009), FOSB (47.63 ± 17. 55 vs 56.06 ± 10.30, p= 0.5320), JUN (7313.90 ± 984.93 vs 11370.09 ± 1286.35, p= 0.2563) JUNB (4745.36 ± 599. 17 vs 5955.45 ± 600.91, p= 0.7620) and JUND (3309. 63 ± 270.64 vs 8057.90 ± 1043.05, p= 0.00006). In additional experiments, we enrolled people with hypertension and phenotype them for SSBP using an established in-patient protocol of salt-loading/depletion and performed single-cell transcriptomic analyses in vivo on PBMCs. We found that expression of the FOS and JUN genes change in concert with blood pressure after salt-loading and depletion in salt-sensitive but not salt-resistant humans. Our findings reveal a role for immune cell AP-1 signaling in salt-sensitive hypertension and may provide a potential target for treatment and diagnosis. Keywords: Activator protein 1 (AP-1), FOS, JUN, Salt-sensitive hypertension, Humans