ArticleCardiovascular research2021
Sodium activates human monocytes via the NADPH oxidase and isolevuglandin formation.
Article in Cardiovascular research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 78 citations in OpenAlex.
- Myeloid Activator Protein-1 Complex Contributes to Salt-Sensitive Hypertension.Circulation research · 2026Article
- Randomized Crossover Trial of Low Sodium Dialysate on Tissue Sodium Accumulation in Hemodialysis.Kidney international reports · 2026Article
- Salt and chronic kidney disease.Nature reviews. Nephrology · 2026Review
- A sodium-HIF1α axis coordinates immune metabolic reprogramming and mitochondrial remodeling in salt-sensitive hypertension.Research square · 2026Article
- Small RNA Sequencing of Human Urinary Extracellular Vesicles Reveals Association of High-Sodium Diet With Renal Proinflammatory Pathways.Journal of the American Heart Association · 2026Article
- High-salt diet aggravates allergic rhinitis through the NFAT5 signaling pathway.NPJ science of food · 2026Article
- Transcriptomic Analysis Reveals Novel Mechanisms Underlying Neutrophil Activation Induced by High Salt.International journal of molecular sciences · 2026Article
- Review
- Animal models of hypertension and concurrent organs injury.Animal models and experimental medicine · 2025Review
- Article
- Epithelial Na+ Channels, Immune Cells, and Salt.Annual review of physiology · 2025Review
- Epigenetic Regulation of Innate and Adaptive Immune Cells in Salt-Sensitive Hypertension.Circulation research · 2025Review
- Intersecting epidemics: immune dysregulation associated with HIV and tuberculosis syndemic contribute to increased risk of hypertensive disease in Sub-Saharan Africa.Frontiers in cardiovascular medicine · 2025Review
- Review of mechanisms and frontier applications in IL-17A-induced hypertension.Open medicine (Warsaw, Poland) · 2025Review
- Reactive oxygen species in hypertension.Nature reviews. Cardiology · 2025Review
- Myeloid-Specific JAK2 Contributes to Inflammation and Salt Sensitivity of Blood Pressure.Circulation research · 2024Article
- Posttranslationally modified self-peptides promote hypertension in mouse models.The Journal of clinical investigation · 2024Article
- Immunological insights into hypertension: unraveling triggers and potential therapeutic avenues.Hypertension research : official journal of the Japanese Society of Hypertension · 2024Review
- Immune Mechanisms in Hypertension.Hypertension (Dallas, Tex. : 1979) · 2024Review
- Myeloid Cell Glucocorticoid, Not Mineralocorticoid Receptor Signaling, Contributes to Salt-Sensitive Hypertension in Humans via Cortisol.bioRxiv : the preprint server for biology · 2024Article
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Authors and funding
22 authors at 3 institutions in 2 countries.
Funding
Abstract
aimsPrior studies have focused on the role of the kidney and vasculature in salt-induced modulation of blood pressure; however, recent data indicate that sodium accumulates in tissues and can activate immune cells. We sought to examine mechanisms by which salt causes activation of human monocytes both in vivo and in vitro. METHODS AND
resultsTo study the effect of salt in human monocytes, monocytes were isolated from volunteers to perform several in vitro experiments. Exposure of human monocytes to elevated Na+ex vivo caused a co-ordinated response involving isolevuglandin (IsoLG)-adduct formation, acquisition of a dendritic cell (DC)-like morphology, expression of activation markers CD83 and CD16, and increased production of pro-inflammatory cytokines tumour necrosis factor-α, interleukin (IL)-6, and IL-1β. High salt also caused a marked change in monocyte gene expression as detected by RNA sequencing and enhanced monocyte migration to the chemokine CC motif chemokine ligand 5. NADPH-oxidase inhibition attenuated monocyte activation and IsoLG-adduct formation. The increase in IsoLG-adducts correlated with risk factors including body mass index, pulse pressure. Monocytes exposed to high salt stimulated IL-17A production from autologous CD4+ and CD8+ T cells. In addition, to evaluate the effect of salt in vivo, monocytes and T cells isolated from humans were adoptively transferred to immunodeficient NSG mice. Salt feeding of humanized mice caused monocyte-dependent activation of human T cells reflected by proliferation and accumulation of T cells in the bone marrow. Moreover, we performed a cross-sectional study in 70 prehypertensive subjects. Blood was collected for flow cytometric analysis and 23Na magnetic resonance imaging was performed for tissue sodium measurements. Monocytes from humans with high skin Na+ exhibited increased IsoLG-adduct accumulation and CD83 expression.
conclusionHuman monocytes exhibit co-ordinated increases in parameters of activation, conversion to a DC-like phenotype and ability to activate T cells upon both in vitro and in vivo sodium exposure. The ability of monocytes to be activated by sodium is related to in vivo cardiovascular disease risk factors. We therefore propose that in addition to the kidney and vasculature, immune cells like monocytes convey salt-induced cardiovascular risk in humans.
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