{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T08:05:26Z","timestamp":1789632326273,"version":"build-2803163510"},"reference-count":30,"publisher":"Portland Press Ltd.","issue":"10","license":[{"start":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:00:00Z","timestamp":1788739200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2021\/08847-9"],"award-info":[{"award-number":["2021\/08847-9"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"HHS | NIH | National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["HL169202"],"award-info":[{"award-number":["HL169202"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,10,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Aldosterone promotes endothelial dysfunction and cardiovascular injury through mineralocorticoid receptor (MR) activation. Autophagy is essential for endothelial homeostasis, yet its role in aldosterone-mediated vascular dysfunction remains unclear. We tested whether aldosterone impairs autophagic flux and whether restoring autophagy via Beclin1 (BCN1) activation protects vascular and cardiac function. Endothelial and vascular responses to aldosterone were assessed in wild-type mice, BCN1 gain-of-function mice (Becn1), and mice treated with spermidine or a BCN1-activating TB-peptide. Vascular function, nitric oxide (NO)\/reactive oxygen species (ROS) production, autophagy markers, endothelial migration, and cardiac fibrosis were evaluated using wire myography, fluorescence assays, western blotting, confocal microscopy, migration assays, and histology. Aldosterone impaired endothelium-dependent relaxation, decreased NO, increased ROS, and impaired autophagic processing in an MR-dependent manner, as indicated by an increased LC3-II\/LC3-I ratio, p62 accumulation, and reduced phosphorylated BCN1. Spermidine restored endothelial function and normalized NO and ROS levels. BCN1 gain-of-function mice were protected from aldosterone-induced endothelial dysfunction and exhibited reduced coronary and myocardial fibrosis. Activation of BCN1 by TB-peptide enhanced autophagic flux improved vascular function, decreased cardiac fibrosis, and rescued endothelial migration impaired by aldosterone. Aldosterone induces endothelial dysfunction by suppressing autophagic flux through MR activation. Genetic or pharmacologic enhancement of BCN1-dependent autophagy restores endothelial homeostasis and prevents vascular and cardiac injury, identifying autophagy activation as a promising therapeutic approach for cardiovascular diseases associated with mineralocorticoid excess.<\/jats:p>","DOI":"10.1042\/cs20260969","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T11:20:27Z","timestamp":1788780027000},"page":"2053-2067","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genetic and pharmacologic activation of BECLIN1 prevents aldosterone-induced cardiovascular damage"],"prefix":"10.1042","volume":"140","author":[{"given":"Rafael\u00a0M.","family":"Costa","sequence":"first","affiliation":[{"name":"1Department of Physiology and Cell Biology, University of South Alabama, Mobile, AL, U.S.A."},{"name":"2Institute of Health Sciences, Federal University of Jatai, Jatai, GO, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariane","family":"Bruder","sequence":"additional","affiliation":[{"name":"1Department of Physiology and Cell Biology, University of South Alabama, Mobile, AL, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliano\u00a0V.","family":"Alves","sequence":"additional","affiliation":[{"name":"2Institute of Health Sciences, Federal University of Jatai, Jatai, GO, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debora\u00a0M.","family":"Cerqueira","sequence":"additional","affiliation":[{"name":"3Department of Pediatrics, University of Pittsburgh, Pittsburgh, PA, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis Oliveira","family":"de Moraes","sequence":"additional","affiliation":[{"name":"1Department of Physiology and Cell Biology, University of South Alabama, Mobile, AL, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tyler","family":"Beling","sequence":"additional","affiliation":[{"name":"1Department of Physiology and Cell Biology, University of South Alabama, Mobile, AL, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Guerrero","sequence":"additional","affiliation":[{"name":"1Department of Physiology and Cell Biology, University of South Alabama, Mobile, AL, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaqueline","family":"Ho","sequence":"additional","affiliation":[{"name":"3Department of Pediatrics, University of Pittsburgh, Pittsburgh, PA, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita\u00a0C.","family":"Tostes","sequence":"additional","affiliation":[{"name":"4Department of Pharmacology, Medical School of Ribeirao Preto at the University of Sao Paulo, Ribeirao Preto, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5671-318X","authenticated-orcid":false,"given":"Thiago","family":"Bruder-Nascimento","sequence":"additional","affiliation":[{"name":"1Department of Physiology and Cell Biology, University of South Alabama, Mobile, AL, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2026,9,17]]},"reference":[{"key":"2026091703415631100_B1","doi-asserted-by":"publisher","first-page":"1899","DOI":"10.1161\/HYPERTENSIONAHA.122.17964","article-title":"Aldosterone as a mediator of cardiovascular damage","volume":"79","author":"Buffolo","year":"2022","journal-title":"Hypertension"},{"key":"2026091703415631100_B2","doi-asserted-by":"publisher","first-page":"1866","DOI":"10.1161\/CIRCULATIONAHA.116.024369","article-title":"NLRP3 inflammasome mediates aldosterone-induced vascular damage","volume":"134","author":"Bruder-Nascimento","year":"2016","journal-title":"Circulation"},{"key":"2026091703415631100_B3","doi-asserted-by":"publisher","first-page":"776","DOI":"10.1161\/HYPERTENSIONAHA.123.21888","article-title":"Role of the CCL5 and its receptor, CCR5, in the genesis of aldosterone-induced hypertension, vascular dysfunction, and end-organ damage","volume":"81","author":"Costa","year":"2024","journal-title":"Hypertension"},{"key":"2026091703415631100_B4","doi-asserted-by":"publisher","first-page":"915","DOI":"10.1161\/HYPERTENSIONAHA.114.01997","article-title":"Endothelial cell mineralocorticoid receptors: turning cardiovascular risk factors into cardiovascular dysfunction","volume":"63","author":"Jaffe","year":"2014","journal-title":"Hypertension"},{"key":"2026091703415631100_B5","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.kisu.2021.11.001","article-title":"Mineralocorticoid receptor activation and antagonism in cardiovascular disease: cellular and molecular mechanisms","volume":"12","author":"Bauersachs","year":"2022","journal-title":"Kidney Int. 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