Chemerin Contributes to Sodium Induced Cardiometabolic Disease and Salt-Sensitive Hypertension in Humans

Salt-sensitivity of blood pressure (SSBP) is characterized by blood pressure (BP) changes in response to dietary sodium and is linked to immune cell infiltration in vascular tissues. Perivascular adipose tissue (PVAT) plays a key role in cellular and physiological processes, with PVAT-derived adipokines implicated in hypertension. However, the role of PVAT-derived adipokines in SSBP in humans remains unexplored. One such adipokine, chemerin, promotes immune cell trafficking and contributes to sodium-induced hypertension in salt-sensitive rodent models. This study aimed to investigate how varying sodium intake influences the expression of chemerin-specific receptors (CMKLR1, GPR1, CCRL2) on human monocytes and how chemerin signaling contributes to changes in BP. We hypothesized that increased sodium intake would upregulate these receptors, leading to increased BP. Using bulk RNA sequencing in isolated human monocytes treated with normal or high sodium, our results demonstrated no expression of GPR1, a decrease in CMKLR1 (6248 ± 3839 vs 3489 ± 2664, P = 0.001), and an increase in CCRL2 (1689 ± 548 vs 2395 ± 726, P = 0.007) expression. We performed a CITE-Seq analysis on PBMCs from hypertensive participants to determine how salt sensitivity affects CMKLR1 and CCRL2 expression. We found that CMKLR1 expression did not differ between salt-sensitive (SS) and salt-resistant (SR) participants (SR: P = 0.561, SS: P = 0.462), however, sodium depletion increased CCRL2 expression in SS participants (P = 0.019) compared to SR participants (P = 0.46). Plasma chemerin levels in hypertensive subjects increased significantly with sodium depletion when compared to base and sodium loading (Base: 26 ± 13 vs SL: 31±10 vs SD: 40 ±13, RM one-way ANOVA P = 0.001). BMI was positively correlated to CMKLR1 expression in monocytes (P = 0.033) and CCRL2 expression in DCs (P = 0.025) when going from sodium loading to depletion. Plasma chemerin was positively correlated to BP during sodium loading (P = 0.017) and depletion (P =0.036), but not at baseline (P = 0.161). Our findings suggest that chemerin and its receptors may play a role in sodium-induced cardiometabolic disease and SSBP. This study was supported by the National Institutes of Health grants R01 HL144941 (AK) D34HP16299, and T32 5T32DK007569-36 (RM) This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.