Chemerin - CMKLR1 signaling contributes to immune metabolic dysfunction in salt-sensitive hypertension.

Authors

Ronald McMillan, Mohammad Saleem, Ariel Thorson, Olivia Pierre-Louis, Selam Desta, Lale A Ertuglu, Celestine N Wanjalla, Lindsey Stolze, Quanhu Sheng, Naome Mwesigwa, Annet Kirabo

Published in

Clinical and experimental hypertension (New York, N.Y. : 1993). Volume 48. Issue 1. Pages 2736024. Dec 31, 2026. Epub Sep 27, 2026.

Abstract

Salt-sensitivity of blood pressure (SSBP) is a significant cardiovascular risk factor, but its underlying immunometabolic mechanisms remain unclear. Chemerin, an adipose-derived inflammatory mediator linked to vascular dysfunction, was studied in 30 hypertensive adults (mean age 53.1 years; 53% female; mean BMI 32.1 kg/m²) during an inpatient salt-sensitivity protocol. Participants underwent salt-loading and salt-depletion phases over three days. Plasma and urine chemerin levels were measured, alongside immune cell phenotyping and transcriptomic profiling using CITE-seq, RNA-seq, and NanoString. Plasma chemerin increased significantly from salt-loading to salt-depletion (100.4 to 125.8 pg/mL; p = 0.008) and was higher in salt-sensitive individuals during depletion (141.2 vs. 108.6 pg/mL; p = 0.02). Plasma chemerin correlated with systolic blood pressure (SBP) during salt depletion (R² = 0.20, p = 0.01), while urinary chemerin increased but did not correlate with SBP. In vitro, high-sodium media suppressed CMKLR1 (chemerin receptor) expression in monocytes (p < 0.01). CITE-seq revealed a 1.8-fold enrichment of CMKLR1 in classical monocytes in salt-resistant individuals compared to salt-sensitive ones, with CMKLR1 inversely correlating with ΔSBP (R² = 0.47, p = 0.03) and ΔMAP (R² = 0.72, p = 0.004). CMKLR1 was linked to glycolytic and oxidative phosphorylation gene upregulation, and its expression in dendritic cells correlated with urinary lactate and fumarate levels. The chemerin-CMKLR1 axis is dysregulated in SSBP, influencing monocyte and dendritic cell metabolism and blood pressure. Chemerin and CMKLR1 may serve as biomarkers and therapeutic targets for salt-sensitive hypertension.

PMID:
42802577
Bibliographic data and abstract were imported from PubMed on 28 Sep 2026.

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