دورية أكاديمية
NLRP3 Inflammasome Mediates Aldosterone-Induced Vascular Damage.
| العنوان: | NLRP3 Inflammasome Mediates Aldosterone-Induced Vascular Damage. |
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| المؤلفون: | Bruder-Nascimento T; From Department of Pharmacology (T.B.-N., N.S.F., C.Z.Z., F.R., I.O.P., V.C.O., K.B.N., R.A.-L., E.C., F.L.M., D.P., J.P.M.L., J.C.A.F., R.C.T.), Department of Physiology (C.A.A.S., R.F.), Department of Biochemistry and Immunology (D.C.), Department of Clinical Medicine, Division of Endocrinology (P.C.E., A.C.M.), and Department of Cell and Molecular Biology (D.S.Z.), Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP, Brazil; Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil (F.V.P., T.B., N.O.); and Department of Pharmacology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil (S.B.C.). bruderthiago@usp.br rtostes@usp.br., Ferreira NS; From Department of Pharmacology (T.B.-N., N.S.F., C.Z.Z., F.R., I.O.P., V.C.O., K.B.N., R.A.-L., E.C., F.L.M., D.P., J.P.M.L., J.C.A.F., R.C.T.), Department of Physiology (C.A.A.S., R.F.), Department of Biochemistry and Immunology (D.C.), Department of Clinical Medicine, Division of Endocrinology (P.C.E., A.C.M.), and Department of Cell and Molecular Biology (D.S.Z.), Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP, Brazil; Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil (F.V.P., T.B., N.O.); and Department of Pharmacology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil (S.B.C.)., Zanotto CZ; From Department of Pharmacology (T.B.-N., N.S.F., C.Z.Z., F.R., I.O.P., V.C.O., K.B.N., R.A.-L., E.C., F.L.M., D.P., J.P.M.L., J.C.A.F., R.C.T.), Department of Physiology (C.A.A.S., R.F.), Department of Biochemistry and Immunology (D.C.), Department of Clinical Medicine, Division of Endocrinology (P.C.E., A.C.M.), and Department of Cell and Molecular Biology (D.S.Z.), Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP, Brazil; Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil (F.V.P., T.B., N.O.); and Department of Pharmacology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil (S.B.C.)., Ramalho F; From Department of Pharmacology (T.B.-N., N.S.F., C.Z.Z., F.R., I.O.P., V.C.O., K.B.N., R.A.-L., E.C., F.L.M., D.P., J.P.M.L., J.C.A.F., R.C.T.), Department of Physiology (C.A.A.S., R.F.), Department of Biochemistry and Immunology (D.C.), Department of Clinical Medicine, Division of Endocrinology (P.C.E., A.C.M.), and Department of Cell and Molecular Biology (D.S.Z.), Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP, Brazil; Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil (F.V.P., T.B., N.O.); and Department of Pharmacology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil (S.B.C.)., Pequeno IO; From Department of Pharmacology (T.B.-N., N.S.F., C.Z.Z., F.R., I.O.P., V.C.O., K.B.N., R.A.-L., E.C., F.L.M., D.P., J.P.M.L., J.C.A.F., R.C.T.), Department of Physiology (C.A.A.S., R.F.), Department of Biochemistry and Immunology (D.C.), Department of Clinical Medicine, Division of Endocrinology (P.C.E., A.C.M.), and Department of Cell and Molecular Biology (D.S.Z.), Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP, Brazil; Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil (F.V.P., T.B., N.O.); and Department of Pharmacology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil (S.B.C.)., Olivon VC; From Department of Pharmacology (T.B.-N., N.S.F., C.Z.Z., F.R., I.O.P., V.C.O., K.B.N., R.A.-L., E.C., F.L.M., D.P., J.P.M.L., J.C.A.F., R.C.T.), Department of Physiology (C.A.A.S., R.F.), Department of Biochemistry and Immunology (D.C.), Department of Clinical Medicine, Division of Endocrinology (P.C.E., A.C.M.), and Department of Cell and Molecular Biology (D.S.Z.), Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP, Brazil; Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil (F.V.P., T.B., N.O.); and Department of Pharmacology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil (S.B.C.)., Neves KB; From Department of Pharmacology (T.B.-N., N.S.F., C.Z.Z., F.R., I.O.P., V.C.O., K.B.N., R.A.-L., E.C., F.L.M., D.P., J.P.M.L., J.C.A.F., R.C.T.), Department of Physiology (C.A.A.S., R.F.), Department of Biochemistry and Immunology (D.C.), Department of Clinical Medicine, Division of Endocrinology (P.C.E., A.C.M.), and Department of Cell and Molecular Biology (D.S.Z.), Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP, Brazil; Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil (F.V.P., T.B., N.O.); and Department of Pharmacology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil (S.B.C.)., Alves-Lopes R; From Department of Pharmacology (T.B.-N., N.S.F., C.Z.Z., F.R., I.O.P., V.C.O., K.B.N., R.A.-L., E.C., F.L.M., D.P., J.P.M.L., J.C.A.F., R.C.T.), Department of Physiology (C.A.A.S., R.F.), Department of Biochemistry and Immunology (D.C.), Department of Clinical Medicine, Division of Endocrinology (P.C.E., A.C.M.), and Department of Cell and Molecular Biology (D.S.Z.), Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP, Brazil; Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil (F.V.P., T.B., N.O.); and Department of Pharmacology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil (S.B.C.)., Campos E; From Department of Pharmacology (T.B.-N., N.S.F., C.Z.Z., F.R., I.O.P., V.C.O., K.B.N., R.A.-L., E.C., F.L.M., D.P., J.P.M.L., J.C.A.F., R.C.T.), Department of Physiology (C.A.A.S., R.F.), Department of Biochemistry and Immunology (D.C.), Department of Clinical Medicine, Division of Endocrinology (P.C.E., A.C.M.), and Department of Cell and Molecular Biology (D.S.Z.), Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP, Brazil; Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil (F.V.P., T.B., N.O.); and Department of Pharmacology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil (S.B.C.)., Silva CA; From Department of Pharmacology (T.B.-N., N.S.F., C.Z.Z., F.R., I.O.P., V.C.O., K.B.N., R.A.-L., E.C., F.L.M., D.P., J.P.M.L., J.C.A.F., R.C.T.), Department of Physiology (C.A.A.S., R.F.), Department of Biochemistry and Immunology (D.C.), Department of Clinical Medicine, Division of Endocrinology (P.C.E., A.C.M.), and Department of Cell and Molecular Biology (D.S.Z.), Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP, Brazil; Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil (F.V.P., T.B., N.O.); and Department of Pharmacology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil (S.B.C.)., Fazan R; From Department of Pharmacology (T.B.-N., N.S.F., C.Z.Z., F.R., I.O.P., V.C.O., K.B.N., R.A.-L., E.C., F.L.M., D.P., J.P.M.L., J.C.A.F., R.C.T.), Department of Physiology (C.A.A.S., R.F.), Department of Biochemistry and Immunology (D.C.), Department of Clinical Medicine, Division of Endocrinology (P.C.E., A.C.M.), and Department of Cell and Molecular Biology (D.S.Z.), Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP, Brazil; Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil (F.V.P., T.B., N.O.); and Department of Pharmacology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil (S.B.C.)., Carlos D; From Department of Pharmacology (T.B.-N., N.S.F., C.Z.Z., F.R., I.O.P., V.C.O., K.B.N., R.A.-L., E.C., F.L.M., D.P., J.P.M.L., J.C.A.F., R.C.T.), Department of Physiology (C.A.A.S., R.F.), Department of Biochemistry and Immunology (D.C.), Department of Clinical Medicine, Division of Endocrinology (P.C.E., A.C.M.), and Department of Cell and Molecular Biology (D.S.Z.), Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP, Brazil; Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil (F.V.P., T.B., N.O.); and Department of Pharmacology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil (S.B.C.)., Mestriner FL; From Department of Pharmacology (T.B.-N., N.S.F., C.Z.Z., F.R., I.O.P., V.C.O., K.B.N., R.A.-L., E.C., F.L.M., D.P., J.P.M.L., J.C.A.F., R.C.T.), Department of Physiology (C.A.A.S., R.F.), Department of Biochemistry and Immunology (D.C.), Department of Clinical Medicine, Division of Endocrinology (P.C.E., A.C.M.), and Department of Cell and Molecular Biology (D.S.Z.), Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP, Brazil; Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil (F.V.P., T.B., N.O.); and Department of Pharmacology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil (S.B.C.)., Prado D; From Department of Pharmacology (T.B.-N., N.S.F., C.Z.Z., F.R., I.O.P., V.C.O., K.B.N., R.A.-L., E.C., F.L.M., D.P., J.P.M.L., J.C.A.F., R.C.T.), Department of Physiology (C.A.A.S., R.F.), Department of Biochemistry and Immunology (D.C.), Department of Clinical Medicine, Division of Endocrinology (P.C.E., A.C.M.), and Department of Cell and Molecular Biology (D.S.Z.), Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP, Brazil; Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil (F.V.P., T.B., N.O.); and Department of Pharmacology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil (S.B.C.)., Pereira FV; From Department of Pharmacology (T.B.-N., N.S.F., C.Z.Z., F.R., I.O.P., V.C.O., K.B.N., R.A.-L., E.C., F.L.M., D.P., J.P.M.L., J.C.A.F., R.C.T.), Department of Physiology (C.A.A.S., R.F.), Department of Biochemistry and Immunology (D.C.), Department of Clinical Medicine, Division of Endocrinology (P.C.E., A.C.M.), and Department of Cell and Molecular Biology (D.S.Z.), Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP, Brazil; Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil (F.V.P., T.B., N.O.); and Department of Pharmacology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil (S.B.C.)., Braga T; From Department of Pharmacology (T.B.-N., N.S.F., C.Z.Z., F.R., I.O.P., V.C.O., K.B.N., R.A.-L., E.C., F.L.M., D.P., J.P.M.L., J.C.A.F., R.C.T.), Department of Physiology (C.A.A.S., R.F.), Department of Biochemistry and Immunology (D.C.), Department of Clinical Medicine, Division of Endocrinology (P.C.E., A.C.M.), and Department of Cell and Molecular Biology (D.S.Z.), Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP, Brazil; Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil (F.V.P., T.B., N.O.); and Department of Pharmacology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil (S.B.C.)., Luiz JP; From Department of Pharmacology (T.B.-N., N.S.F., C.Z.Z., F.R., I.O.P., V.C.O., K.B.N., R.A.-L., E.C., F.L.M., D.P., J.P.M.L., J.C.A.F., R.C.T.), Department of Physiology (C.A.A.S., R.F.), Department of Biochemistry and Immunology (D.C.), Department of Clinical Medicine, Division of Endocrinology (P.C.E., A.C.M.), and Department of Cell and Molecular Biology (D.S.Z.), Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP, Brazil; Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil (F.V.P., T.B., N.O.); and Department of Pharmacology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil (S.B.C.)., Cau SB; From Department of Pharmacology (T.B.-N., N.S.F., C.Z.Z., F.R., I.O.P., V.C.O., K.B.N., R.A.-L., E.C., F.L.M., D.P., J.P.M.L., J.C.A.F., R.C.T.), Department of Physiology (C.A.A.S., R.F.), Department of Biochemistry and Immunology (D.C.), Department of Clinical Medicine, Division of Endocrinology (P.C.E., A.C.M.), and Department of Cell and Molecular Biology (D.S.Z.), Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP, Brazil; Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil (F.V.P., T.B., N.O.); and Department of Pharmacology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil (S.B.C.)., Elias PC; From Department of Pharmacology (T.B.-N., N.S.F., C.Z.Z., F.R., I.O.P., V.C.O., K.B.N., R.A.-L., E.C., F.L.M., D.P., J.P.M.L., J.C.A.F., R.C.T.), Department of Physiology (C.A.A.S., R.F.), Department of Biochemistry and Immunology (D.C.), Department of Clinical Medicine, Division of Endocrinology (P.C.E., A.C.M.), and Department of Cell and Molecular Biology (D.S.Z.), Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP, Brazil; Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil (F.V.P., T.B., N.O.); and Department of Pharmacology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil (S.B.C.)., Moreira AC; From Department of Pharmacology (T.B.-N., N.S.F., C.Z.Z., F.R., I.O.P., V.C.O., K.B.N., R.A.-L., E.C., F.L.M., D.P., J.P.M.L., J.C.A.F., R.C.T.), Department of Physiology (C.A.A.S., R.F.), Department of Biochemistry and Immunology (D.C.), Department of Clinical Medicine, Division of Endocrinology (P.C.E., A.C.M.), and Department of Cell and Molecular Biology (D.S.Z.), Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP, Brazil; Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil (F.V.P., T.B., N.O.); and Department of Pharmacology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil (S.B.C.)., Câmara NO; From Department of Pharmacology (T.B.-N., N.S.F., C.Z.Z., F.R., I.O.P., V.C.O., K.B.N., R.A.-L., E.C., F.L.M., D.P., J.P.M.L., J.C.A.F., R.C.T.), Department of Physiology (C.A.A.S., R.F.), Department of Biochemistry and Immunology (D.C.), Department of Clinical Medicine, Division of Endocrinology (P.C.E., A.C.M.), and Department of Cell and Molecular Biology (D.S.Z.), Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP, Brazil; Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil (F.V.P., T.B., N.O.); and Department of Pharmacology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil (S.B.C.)., Zamboni DS; From Department of Pharmacology (T.B.-N., N.S.F., C.Z.Z., F.R., I.O.P., V.C.O., K.B.N., R.A.-L., E.C., F.L.M., D.P., J.P.M.L., J.C.A.F., R.C.T.), Department of Physiology (C.A.A.S., R.F.), Department of Biochemistry and Immunology (D.C.), Department of Clinical Medicine, Division of Endocrinology (P.C.E., A.C.M.), and Department of Cell and Molecular Biology (D.S.Z.), Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP, Brazil; Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil (F.V.P., T.B., N.O.); and Department of Pharmacology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil (S.B.C.)., Alves-Filho JC; From Department of Pharmacology (T.B.-N., N.S.F., C.Z.Z., F.R., I.O.P., V.C.O., K.B.N., R.A.-L., E.C., F.L.M., D.P., J.P.M.L., J.C.A.F., R.C.T.), Department of Physiology (C.A.A.S., R.F.), Department of Biochemistry and Immunology (D.C.), Department of Clinical Medicine, Division of Endocrinology (P.C.E., A.C.M.), and Department of Cell and Molecular Biology (D.S.Z.), Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP, Brazil; Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil (F.V.P., T.B., N.O.); and Department of Pharmacology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil (S.B.C.)., Tostes RC; From Department of Pharmacology (T.B.-N., N.S.F., C.Z.Z., F.R., I.O.P., V.C.O., K.B.N., R.A.-L., E.C., F.L.M., D.P., J.P.M.L., J.C.A.F., R.C.T.), Department of Physiology (C.A.A.S., R.F.), Department of Biochemistry and Immunology (D.C.), Department of Clinical Medicine, Division of Endocrinology (P.C.E., A.C.M.), and Department of Cell and Molecular Biology (D.S.Z.), Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP, Brazil; Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil (F.V.P., T.B., N.O.); and Department of Pharmacology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil (S.B.C.). bruderthiago@usp.br rtostes@usp.br. |
| المصدر: | Circulation [Circulation] 2016 Dec 06; Vol. 134 (23), pp. 1866-1880. Date of Electronic Publication: 2016 Nov 01. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Lippincott Williams & Wilkins Country of Publication: United States NLM ID: 0147763 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1524-4539 (Electronic) Linking ISSN: 00097322 NLM ISO Abbreviation: Circulation Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Hagerstown, MD : Lippincott Williams & Wilkins Original Publication: [Dallas, Tex., etc., American Heart Association, etc.] |
| مواضيع طبية MeSH: | Aldosterone/*pharmacology , Mesenteric Arteries/*drug effects , NLR Family, Pyrin Domain-Containing 3 Protein/*metabolism, Acetylcholine/pharmacology ; Animals ; Bone Marrow Cells/cytology ; Bone Marrow Transplantation ; Caspase 1/deficiency ; Caspase 1/genetics ; Humans ; Intercellular Adhesion Molecule-1/genetics ; Intercellular Adhesion Molecule-1/metabolism ; Interleukin-1beta/blood ; Leukocytes, Mononuclear/cytology ; Leukocytes, Mononuclear/drug effects ; Leukocytes, Mononuclear/metabolism ; Macrophages/cytology ; Macrophages/drug effects ; Macrophages/metabolism ; Male ; Mesenteric Arteries/physiology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; NF-kappa B/metabolism ; NLR Family, Pyrin Domain-Containing 3 Protein/deficiency ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics ; Nigericin/pharmacology ; Reactive Oxygen Species/metabolism ; Receptors, Interleukin-1/deficiency ; Receptors, Interleukin-1/genetics ; Signal Transduction/drug effects ; Vascular Diseases/chemically induced |
| مستخلص: | Background: Inflammation is a key feature of aldosterone-induced vascular damage and dysfunction, but molecular mechanisms by which aldosterone triggers inflammation remain unclear. The NLRP3 inflammasome is a pivotal immune sensor that recognizes endogenous danger signals triggering sterile inflammation. Methods: We analyzed vascular function and inflammatory profile of wild-type (WT), NLRP3 knockout (NLRP3 -/- ), caspase-1 knockout (Casp-1 -/- ), and interleukin-1 receptor knockout (IL-1R -/- ) mice treated with vehicle or aldosterone (600 µg·kg -1 ·d -1 for 14 days through osmotic mini-pump) while receiving 1% saline to drink. Results: Here, we show that NLRP3 inflammasome plays a central role in aldosterone-induced vascular dysfunction. Long-term infusion of aldosterone in mice resulted in elevation of plasma interleukin-1β levels and vascular abnormalities. Mice lacking the IL-1R or the inflammasome components NLRP3 and caspase-1 were protected from aldosterone-induced vascular damage. In vitro, aldosterone stimulated NLRP3-dependent interleukin-1β secretion by bone marrow-derived macrophages by activating nuclear factor-κB signaling and reactive oxygen species generation. Moreover, chimeric mice reconstituted with NLRP3-deficient hematopoietic cells showed that NLRP3 in immune cells mediates aldosterone-induced vascular damage. In addition, aldosterone increased the expression of NLRP3, active caspase-1, and mature interleukin-1β in human peripheral blood mononuclear cells. Hypertensive patients with hyperaldosteronism or normal levels of aldosterone exhibited increased activity of NLRP3 inflammasome, suggesting that the effect of hyperaldosteronism on the inflammasome may be mediated through high blood pressure. Conclusions: Together, these data demonstrate that NLRP3 inflammasome, through activation of IL-1R, is critically involved in the deleterious vascular effects of aldosterone, placing NLRP3 as a potential target for therapeutic interventions in conditions with high aldosterone levels. (© 2016 American Heart Association, Inc.) |
| فهرسة مساهمة: | Keywords: aldosterone; immunology; inflammasomes; inflammation |
| المشرفين على المادة: | 0 (Icam1 protein, mouse) 0 (Interleukin-1beta) 0 (NF-kappa B) 0 (NLR Family, Pyrin Domain-Containing 3 Protein) 0 (Nlrp3 protein, mouse) 0 (Reactive Oxygen Species) 0 (Receptors, Interleukin-1) 126547-89-5 (Intercellular Adhesion Molecule-1) 4964P6T9RB (Aldosterone) EC 3.4.22.36 (Caspase 1) N9YNS0M02X (Acetylcholine) RRU6GY95IS (Nigericin) |
| تواريخ الأحداث: | Date Created: 20161103 Date Completed: 20170503 Latest Revision: 20220408 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1161/CIRCULATIONAHA.116.024369 |
| PMID: | 27803035 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1524-4539 |
|---|---|
| DOI: | 10.1161/CIRCULATIONAHA.116.024369 |