ArticleCirculation research2022
DC ENaC-Dependent Inflammasome Activation Contributes to Salt-Sensitive Hypertension.
Article in Circulation research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.
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Who cites it
77 citing papers in PubMed, 88 citations in OpenAlex.
- Magnesium and blood pressure regulation: systemic and renal mechanisms.Hypertension research : official journal of the Japanese Society of Hypertension · 2026Review
- High-Salt Diet Exacerbates Murine Imiquimod-Induced Psoriasis-like Dermatitis via Activation of Serum- and Glucocorticoid-Inducible Kinase 1.International journal of molecular sciences · 2026Article
- 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
- Pathophysiological Mechanisms and Clinical Controversies of Sodium-Induced Hypertension: A Multi-Systemic Perspective.Nutrients · 2026Review
- Myeloid cell renin-angiotensin-aldosterone system in hypertension and inflammation.Current opinion in physiology · 2026Article
- A sodium-HIF1α axis coordinates immune metabolic reprogramming and mitochondrial remodeling in salt-sensitive hypertension.Research square · 2026Article
- Antigen-Presenting Cell Isolevuglandins Link Salt Sensitivity of Blood Pressure to Insulin Resistance.The Journal of clinical endocrinology and metabolism · 2026Article
- The SGK1/ENaC axis in renal injury during salt-sensitive hypertension: from sodium sensing to inflammation.Frontiers in immunology · 2026Review
- The multifaceted impact of a high-salt environment on the immune system and its contribution to salt-sensitive hypertension.Biochemistry and biophysics reports · 2025Review
- Integrated mechanisms linking sodium-potassium imbalance to salt-sensitive hypertension.Physiological reports · 2025Review
- Platelet-to-high-density lipoprotein cholesterol ratio as a potential mediator in the obesity-chronic kidney disease association among hypertensive patients.Renal failure · 2025Article
- Resistance to doxorubicin-induced proteinuria and proteolytic activation of ENaC in 129S2/SvPas mice.Physiological reports · 2025Article
- Mechanisms of NLRP3 inflammasome in chronic kidney disease and the effects of traditional Chinese medicines.Renal failure · 2025Review
- Isolevuglandins Modulate Histone H1 in Myeloid Cells in Salt-Sensitive Hypertension.Circulation research · 2025Article
- Central nervous system mechanisms of salt-sensitive hypertension.Physiological reviews · 2025Review
- Animal models of hypertension and concurrent organs injury.Animal models and experimental medicine · 2025Review
- Salt-Induced Vascular Damage in Hypertension Involves Redox Activation of PARP/TRPM2 Signaling and Inflammasome Assembly.American journal of hypertension · 2025Article
- [Mechanisms of pyroptosis in metabolic diseases].Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2025Review
17 more citing papers are in PubMed but not listed here.
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Authors and funding
19 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundSalt sensitivity of blood pressure is an independent predictor of cardiovascular morbidity and mortality. The exact mechanism by which salt intake increases blood pressure and cardiovascular risk is unknown. We previously found that sodium entry into antigen-presenting cells (APCs) via the amiloride-sensitive epithelial sodium channel EnaC (epithelial sodium channel) leads to the formation of IsoLGs (isolevuglandins) and release of proinflammatory cytokines to activate T cells and modulate salt-sensitive hypertension. In the current study, we hypothesized that ENaC-dependent entry of sodium into APCs activates the NLRP3 (NOD [nucleotide-binding and oligomerization domain]-like receptor family pyrin domain containing 3) inflammasome via IsoLG formation leading to salt-sensitive hypertension.
methodsWe performed RNA sequencing on human monocytes treated with elevated sodium in vitro and Cellular Indexing of Transcriptomes and Epitopes by Sequencing analysis of peripheral blood mononuclear cells from participants rigorously phenotyped for salt sensitivity of blood pressure using an established inpatient protocol. To determine mechanisms, we analyzed inflammasome activation in mouse models of deoxycorticosterone acetate salt-induced hypertension as well as salt-sensitive mice with ENaC inhibition or expression, IsoLG scavenging, and adoptive transfer of wild-type dendritic cells into NLRP3 deficient mice.
resultsWe found that high levels of salt exposure upregulates the NLRP3 inflammasome, pyroptotic and apoptotic caspases, and IL (interleukin)-1β transcription in human monocytes. Cellular Indexing of Transcriptomes and Epitopes by Sequencing revealed that components of the NLRP3 inflammasome and activation marker IL-1β dynamically vary with changes in salt loading/depletion. Mechanistically, we found that sodium-induced activation of the NLRP3 inflammasome is ENaC and IsoLG dependent. NLRP3 deficient mice develop a blunted hypertensive response to elevated sodium, and this is restored by the adoptive transfer of NLRP3 replete APCs.
conclusionsThese findings reveal a mechanistic link between ENaC, inflammation, and salt-sensitive hypertension involving NLRP3 inflammasome activation in APCs. APC activation via the NLRP3 inflammasome can serve as a potential diagnostic biomarker for salt sensitivity of blood pressure.
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