{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T17:03:37Z","timestamp":1793120617845,"version":"4.5.0"},"reference-count":42,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2019,12,8]],"date-time":"2019-12-08T00:00:00Z","timestamp":1575763200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2013\/08216-2"],"award-info":[{"award-number":["2013\/08216-2"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","award":["001"],"award-info":[{"award-number":["001"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Aldosterone excess aggravates endothelial dysfunction in diabetes and hypertension by promoting the increased generation of reactive oxygen species, inflammation, and insulin resistance. Aldosterone activates the molecular platform inflammasome in immune system cells and contributes to vascular dysfunction induced by the mineralocorticoid hormone. It is unclear as to whether the NLRP3 inflammasome associated with the mineralocorticoid receptor contributes to vascular dysfunction in diabetic conditions. Here, we tested the hypothesis that an excess of aldosterone induces vascular dysfunction in type 2 diabetes, via the activation of mineralocorticoid receptors (MR) and assembly of the NLRP3 inflammasome. Mesenteric resistance arteries from control (db\/m) and diabetic (db\/db) mice treated with vehicle, spironolactone (MR antagonist) or an NLRP3 selective inhibitor (MCC950) were used to determine whether NLRP3 contributes to diabetes-associated vascular dysfunction. Db\/db mice exhibited increased vascular expression\/activation of caspase-1 and IL-1\u03b2, increased plasma IL-1\u03b2 levels, active caspase-1 in peritoneal macrophages, and reduced acetylcholine (ACh) vasodilation, compared to db\/m mice. Treatment of db\/db mice with spironolactone and MCC950 decreased plasma IL-1\u03b2 and partly restored ACh vasodilation. Spironolactone also reduced active caspase-1-positive macrophages in db\/db mice, events that contribute to diabetes-associated vascular changes. These data clearly indicate that MR and NLRP3 activation contribute to diabetes-associated vascular dysfunction and pro-inflammatory phenotype.<\/jats:p>","DOI":"10.3390\/cells8121595","type":"journal-article","created":{"date-parts":[[2019,12,9]],"date-time":"2019-12-09T05:54:51Z","timestamp":1575870891000},"page":"1595","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":67,"title":["NLRP3 Inflammasome and Mineralocorticoid Receptors Are Associated with Vascular Dysfunction in Type 2 Diabetes Mellitus"],"prefix":"10.3390","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4648-6694","authenticated-orcid":false,"given":"Nathanne Santos","family":"Ferreira","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto 14040-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thiago","family":"Bruder-Nascimento","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto 14040-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camila Andr\u00e9","family":"Pereira","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto 14040-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camila Zillioto","family":"Zanotto","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto 14040-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas Silva","family":"Prado","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto 14040-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6623-7946","authenticated-orcid":false,"given":"Josiane Fernandes","family":"Silva","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto 14040-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4843-8015","authenticated-orcid":false,"given":"Diane Meyre","family":"Rassi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto 14040-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Cristina","family":"Foss-Freitas","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto 14040-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose Carlos","family":"Alves-Filho","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto 14040-900, Brazil"},{"name":"Department of Biochemistry and Immunology Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto 14040-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Carlos","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Immunology Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto 14040-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9446-0707","authenticated-orcid":false,"given":"Rita de C\u00e1ssia","family":"Tostes","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto 14040-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,12,8]]},"reference":[{"key":"ref_1","unstructured":"I.D.F. 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