Dendritic cell epithelial sodium channel induced inflammation and salt-sensitive hypertension

Abstract

Purpose of review Salt sensitivity of blood pressure (SSBP) is an independent risk factor for cardiovascular disease. Epithelial sodium channel (ENaC) plays a critical role in renal electrolyte and volume regulation and has been implicated in the pathogenesis of SSBP. This review describes recent advances regarding the role of ENaC-dependent inflammation in the development of SSBP. Recent findings We recently found that sodium enters dendritic cells via ENaC, a process regulated by serum/glucocorticoid-regulated kinase 1 and epoxyeicosatrienoic acid 14,15. Sodium entry activates NADPH oxidase, leading to the production of isolevuglandins (IsoLGs). IsoLGs adduct self-proteins to form neoantigens in dendritic cells that activate T cells and result in the release of cytokines promoting sodium retention, kidney damage, and endothelial dysfunction in SSBP. Additionally, we described a novel mechanistic pathway involving ENaC and IsoLG-dependent NLRP3 inflammasome activation. These findings hold promise for the development of novel diagnostic biomarkers and therapeutic options for SSBP. Summary The exact mechanisms underlying SSBP remain elusive. Recent advances in understanding the extrarenal role of ENaC have opened a new perspective, and further research efforts should focus on understanding the link between ENaC, inflammation, and SSBP.