ArticleCirculation research2024
Myeloid-Specific JAK2 Contributes to Inflammation and Salt Sensitivity of Blood Pressure.
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Article in Circulation research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13citing papers in PubMed
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Who cites it
13 citing papers in PubMed.
- Myeloid Activator Protein-1 Complex Contributes to Salt-Sensitive Hypertension.Circulation research · 2026Article
- Metabolic-inflammatory memory: the common pathological basis and therapeutic targets of metabolic syndrome.Reviews in endocrine & metabolic disorders · 2026Review
- The SGK1/ENaC axis in renal injury during salt-sensitive hypertension: from sodium sensing to inflammation.Frontiers in immunology · 2026Review
- Editorial: Salt-sensitive hypertension: mechanisms, therapeutics, and beyond.Frontiers in pharmacology · 2026Article
- The multifaceted impact of a high-salt environment on the immune system and its contribution to salt-sensitive hypertension.Biochemistry and biophysics reports · 2025Review
- JAK2 46/1 (GGCC) Haplotype in Oncogenesis, as Risk Stratifier, and Indicator for Drug Resistance in Myeloproliferative Neoplasms.International journal of molecular sciences · 2025Review
- Single-cell RNA sequencing reveals that a high salt diet increases IL6R-JAK1-STAT3 gene signaling pathway activity in intestinal B cells and Tfh cells of salt-sensitive hypertension animal model.Scientific reports · 2025Article
- IRF5 Mediates Artery Inflammation in Salt-Sensitive Hypertension by Regulating STAT1 and STAT2 Phosphorylation to Increase ESM1 Transcription: Insights from Bioinformatics and Mechanistic Analysis.International journal of molecular sciences · 2025Article
- Epigenetic Regulation of Innate and Adaptive Immune Cells in Salt-Sensitive Hypertension.Circulation research · 2025Review
- The immune-microbiome axis in salt-sensitive hypertension: a focus on renal and neural mechanisms.Frontiers in physiology · 2025Review
- Review of mechanisms and frontier applications in IL-17A-induced hypertension.Open medicine (Warsaw, Poland) · 2025Review
- How PPAR-alpha mediated inflammation may affect the pathophysiology of chronic kidney disease.Current research in physiology · 2025Review
- Salt's Sex-Specific Impact of Gut Microbiota in Hypertension.Circulation research · 2024Article
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Authors and funding
28 authors.
Mohammad SaleemDepartment of Medicine, Division of Clinical Pharmacology (M.S., L.A.A., A.L.M., L.A.E., J.H.P., J.A.I., C.L.L., C.N.W., N.d.l.V., P.D.K., T.A., A.P.H., J.Y., M.K.G., S.Y., A.K.), Vanderbilt University Medical Center, Nashville, TN.ORCID 0000-0001-8091-8361
Luul A AdenDepartment of Medicine, Division of Clinical Pharmacology (M.S., L.A.A., A.L.M., L.A.E., J.H.P., J.A.I., C.L.L., C.N.W., N.d.l.V., P.D.K., T.A., A.P.H., J.Y., M.K.G., S.Y., A.K.), Vanderbilt University Medical Center, Nashville, TN.ORCID 0000-0002-9483-860X
Ashley L MutchlerDepartment of Medicine, Division of Clinical Pharmacology (M.S., L.A.A., A.L.M., L.A.E., J.H.P., J.A.I., C.L.L., C.N.W., N.d.l.V., P.D.K., T.A., A.P.H., J.Y., M.K.G., S.Y., A.K.), Vanderbilt University Medical Center, Nashville, TN.
Chitra BasuDepartment of Medicine, Division of Genetic Medicine (C.B., E.R.G.), Vanderbilt University Medical Center, Nashville, TN.
Lale A ErtugluDepartment of Medicine, Division of Clinical Pharmacology (M.S., L.A.A., A.L.M., L.A.E., J.H.P., J.A.I., C.L.L., C.N.W., N.d.l.V., P.D.K., T.A., A.P.H., J.Y., M.K.G., S.Y., A.K.), Vanderbilt University Medical Center, Nashville, TN.ORCID 0000-0002-6318-4199
Quanhu ShengDepartment of Biostatistics (Q.S.), Vanderbilt University Medical Center, Nashville, TN.ORCID 0000-0001-8951-9295
Niki PennerDivision of Allergy, Pulmonary, and Critical Care Medicine (N.P., A.R.H.).
Anna R HemnesDivision of Allergy, Pulmonary, and Critical Care Medicine (N.P., A.R.H.).ORCID 0000-0002-2755-5845
Jennifer H ParkDepartment of Medicine, Division of Clinical Pharmacology (M.S., L.A.A., A.L.M., L.A.E., J.H.P., J.A.I., C.L.L., C.N.W., N.d.l.V., P.D.K., T.A., A.P.H., J.Y., M.K.G., S.Y., A.K.), Vanderbilt University Medical Center, Nashville, TN.
Jeanne A IshimweDepartment of Medicine, Division of Clinical Pharmacology (M.S., L.A.A., A.L.M., L.A.E., J.H.P., J.A.I., C.L.L., C.N.W., N.d.l.V., P.D.K., T.A., A.P.H., J.Y., M.K.G., S.Y., A.K.), Vanderbilt University Medical Center, Nashville, TN.ORCID 0000-0002-5479-7284
Cheryl L LafferDepartment of Medicine, Division of Clinical Pharmacology (M.S., L.A.A., A.L.M., L.A.E., J.H.P., J.A.I., C.L.L., C.N.W., N.d.l.V., P.D.K., T.A., A.P.H., J.Y., M.K.G., S.Y., A.K.), Vanderbilt University Medical Center, Nashville, TN.ORCID 0000-0002-6453-6010
Fernando ElijovichORCID 0000-0002-2511-056X
Celestine N WanjallaDepartment of Medicine, Division of Clinical Pharmacology (M.S., L.A.A., A.L.M., L.A.E., J.H.P., J.A.I., C.L.L., C.N.W., N.d.l.V., P.D.K., T.A., A.P.H., J.Y., M.K.G., S.Y., A.K.), Vanderbilt University Medical Center, Nashville, TN.ORCID 0000-0001-9159-5414
Nestor de la VisitacionDepartment of Medicine, Division of Clinical Pharmacology (M.S., L.A.A., A.L.M., L.A.E., J.H.P., J.A.I., C.L.L., C.N.W., N.d.l.V., P.D.K., T.A., A.P.H., J.Y., M.K.G., S.Y., A.K.), Vanderbilt University Medical Center, Nashville, TN.ORCID 0000-0001-7229-9601
Paul D KastnerDepartment of Medicine, Division of Clinical Pharmacology (M.S., L.A.A., A.L.M., L.A.E., J.H.P., J.A.I., C.L.L., C.N.W., N.d.l.V., P.D.K., T.A., A.P.H., J.Y., M.K.G., S.Y., A.K.), Vanderbilt University Medical Center, Nashville, TN.ORCID 0009-0003-2074-0380
Claude F AlbrittonSchool of Graduate Studies, Meharry Medical College, Nashville, TN (C.F.A.).ORCID 0000-0002-6891-8737
Taseer AhmadDepartment of Medicine, Division of Clinical Pharmacology (M.S., L.A.A., A.L.M., L.A.E., J.H.P., J.A.I., C.L.L., C.N.W., N.d.l.V., P.D.K., T.A., A.P.H., J.Y., M.K.G., S.Y., A.K.), Vanderbilt University Medical Center, Nashville, TN.ORCID 0000-0003-4545-9598
Alexandria P HaynesDepartment of Medicine, Division of Clinical Pharmacology (M.S., L.A.A., A.L.M., L.A.E., J.H.P., J.A.I., C.L.L., C.N.W., N.d.l.V., P.D.K., T.A., A.P.H., J.Y., M.K.G., S.Y., A.K.), Vanderbilt University Medical Center, Nashville, TN.ORCID 0009-0004-3723-0325
Justin YuDepartment of Medicine, Division of Clinical Pharmacology (M.S., L.A.A., A.L.M., L.A.E., J.H.P., J.A.I., C.L.L., C.N.W., N.d.l.V., P.D.K., T.A., A.P.H., J.Y., M.K.G., S.Y., A.K.), Vanderbilt University Medical Center, Nashville, TN.ORCID 0009-0004-6400-5633
Meghan K GraberDepartment of Medicine, Division of Clinical Pharmacology (M.S., L.A.A., A.L.M., L.A.E., J.H.P., J.A.I., C.L.L., C.N.W., N.d.l.V., P.D.K., T.A., A.P.H., J.Y., M.K.G., S.Y., A.K.), Vanderbilt University Medical Center, Nashville, TN.ORCID 0009-0007-4096-4751
Sharia YasminDepartment of Medicine, Division of Clinical Pharmacology (M.S., L.A.A., A.L.M., L.A.E., J.H.P., J.A.I., C.L.L., C.N.W., N.d.l.V., P.D.K., T.A., A.P.H., J.Y., M.K.G., S.Y., A.K.), Vanderbilt University Medical Center, Nashville, TN.ORCID 0000-0002-8452-405X
Kay-Uwe WagnerWayne State University, Department of Oncology and Tumor Biology Program, Barbara Ann Karmanos Cancer Institute, Detroit, MI (K.-U.W.).ORCID 0000-0002-5081-0226
Peter P SayeskiCenter for Integrative Cardiovascular and Metabolic Disease, University of Florida, Gainesville (P.P.S.).
Antonis K HatzopoulosDepartment of Medicine, Division of Cardiovascular Medicine (C.B., A.K.H.), Vanderbilt University Medical Center, Nashville, TN.
Eric R GamazonDepartment of Medicine, Division of Genetic Medicine (C.B., E.R.G.), Vanderbilt University Medical Center, Nashville, TN.
Alexander G BickDivision of Genetic Medicine (A.G.B.), Vanderbilt University Medical Center, Nashville, TN.ORCID 0000-0001-5824-9595
Thomas R KleymanRenal-Electrolyte Division, Department of Medicine, University of Pittsburgh, PA (T.R.K.).ORCID 0000-0002-2413-5415
Annet KiraboDepartment of Medicine, Division of Clinical Pharmacology (M.S., L.A.A., A.L.M., L.A.E., J.H.P., J.A.I., C.L.L., C.N.W., N.d.l.V., P.D.K., T.A., A.P.H., J.Y., M.K.G., S.Y., A.K.), Vanderbilt University Medical Center, Nashville, TN.ORCID 0000-0001-8580-9359
Funding
Vanderbilt Institute for Clinical and Translational Research (VICTR) -Identifying correlates of functional immunity in SARS-CoV-2 convalescent plasmaUL1TR002243 · NCATS · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Paul A. Harris, Wesley H Self · 2017 to 2026
$130.7MVanderbilt Diabetes Research CenterP30DK020593 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI John Michael Stafford · 2012 to 2026
$29.3MVanderbilt Mouse Metabolic Physiology CenterU24DK059637 · NIDDK · VANDERBILT UNIVERSITY · PI WASSERMAN, DAVID H · 2001 to 2015
$14.9MResource Development CoreU54DK137329 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Thomas R Kleyman · 2023 to 2026
$4.8MENaC regulation and its role in blood pressure homeostasisR01HL147818 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Annet Kirabo, Thomas R Kleyman · 2019 to 2026
$4.6MImmune Mechanisms of Salt-Sensitive hypertensionR01HL144941 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI KIRABO, ANNET · 2021 to 2025
$3.0MSalt Mediated Cross Talk Between Lymphatic Vessels and Immune Cells in Kidney DiseaseR01DK135764 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI VALENTINA KON, Annet Kirabo · 2023 to 2026
$2.9MVanderbilt Hypertension and Blood Pressure Regulation ProgramT32HL144446 · NHLBI · VANDERBILT UNIVERSITY · PI HARRISON, DAVID G · 2019 to 2023
$1.7MFunctional heterogeneity of cardiac reparative cells after injuryR01HL138519 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI HATZOPOULOS, ANTONIS · 2017 to 2020
$1.6MAdvancing drug repositioning and development for Alzheimer's Disease using functional genomics and computational phenomicsR56AG068026 · NIA · VANDERBILT UNIVERSITY MEDICAL CENTER · PI GAMAZON, ERIC R · 2021 to 2022
$1.5MAnti-cytomegalovirus Immune Responses in Atherosclerotic Cardiovascular Disease in Persons Living with HIVK23HL156759 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI WANJALLA, CELESTINE N · 2021 to 2025
$860kSalt taste sensitivity, genetics and salt sensitivity of blood pressure in HIVR21TW012635 · FIC · VANDERBILT UNIVERSITY MEDICAL CENTER · PI KIRABO, ANNET, MASENGA, SEPISO KENIAS · 2023 to 2024
$385kAmerican Heart Association-American Stroke Association 23CDA1053072FIC NIH HHS R21 TW012635NCATS NIH HHS UL1 TR002243NHLBI NIH HHS K23 HL156759NHLBI NIH HHS R01 HL138519NHLBI NIH HHS R01 HL144941NHLBI NIH HHS R01 HL147818NHLBI NIH HHS R03 HL155041NHLBI NIH HHS T32 HL144446NIA NIH HHS R56 AG068026NIDDK NIH HHS P30 DK020593NIDDK NIH HHS R01 DK135764NIDDK NIH HHS U24 DK059637NIDDK NIH HHS U54 DK137329
Abstract
backgroundSalt sensitivity of blood pressure (SSBP), characterized by acute changes in blood pressure with changes in dietary sodium intake, is an independent risk factor for cardiovascular disease and mortality in people with and without hypertension. We previously found that elevated sodium concentration activates antigen-presenting cells (APCs), resulting in high blood pressure, but the mechanisms are unknown. Here, we hypothesized that APC-specific JAK2 (Janus kinase 2) through STAT3 (signal transducer and activator of transcription 3) and SMAD3 (small mothers against decapentaplegic homolog 3) contributes to SSBP.
methodsWe performed bulk or single-cell transcriptomic analyses following in vitro monocytes exposed to high salt and in vivo high sodium treatment in humans using a rigorous salt-loading/depletion protocol to phenotype SSBP. We also used a myeloid cell-specific CD11c
resultsWe found that high salt treatment upregulates gene expression of the JAK/STAT/SMAD pathway while downregulating inhibitors of this pathway, such as suppression of cytokine signaling and cytokine-inducible SH2, in human monocytes. Expression of the JAK2 pathway genes mirrored changes in blood pressure after salt loading and depletion in salt-sensitive but not salt-resistant humans. Ablation of JAK2, specifically in CD11c
conclusionsOur findings reveal the APC JAK2 signaling pathway as a potential target for the diagnosis and treatment of SSBP in humans.
Indexed as
Blood PressureHypertensionJanus Kinase 2Mice, KnockoutSodium Chloride, DietarySTAT3 Transcription FactorAnimalsFemaleHumansInflammationMaleMiceMice, Inbred C57BLMonocytesMyeloid CellsSmad3 ProteinJAK2 protein, humanJak2 protein, mouseJanus Kinase 2Smad3 ProteinSmad3 protein, mouseSodium Chloride, DietarySTAT3 protein, humanStat3 protein, mouseSTAT3 Transcription Factorblood pressurehypertensionJanus kinase 2Smad proteinsSTAT3 transcription factor
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