{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T11:04:30Z","timestamp":1785323070623,"version":"3.55.0"},"posted":{"date-parts":[[2026,7,26]]},"group-title":"Physiology","reference-count":28,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,7,26]],"date-time":"2026-07-26T00:00:00Z","timestamp":1785024000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,7,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/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.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Aldosterone impaired endothelium-dependent relaxation, decreased NO, increased ROS, and disrupted autophagic flux in an MR-dependent manner, indicated by LC3 accumulation and reduced p62 and BCN1 expression. 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. TB-peptide activation of BCN1 enhanced autophagic flux, improved vascular function, decreased cardiac fibrosis, and rescued endothelial migration impaired by aldosterone.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>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>\n                <\/jats:sec>","DOI":"10.64898\/2026.07.22.740044","type":"posted-content","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T05:33:44Z","timestamp":1785130424000},"source":"Crossref","is-referenced-by-count":0,"title":["GENETIC AND PHARMACOLOGIC ACTIVATION OF BECLIN1 PREVENTS ALDOSTERONE-INDUCED CARDIOVASCULAR DAMAGE"],"prefix":"10.64898","author":[{"given":"Rafael M","family":"Costa","sequence":"first","affiliation":[{"name":"Department of Physiology and Cell Biology, University of South Alabama, Mobile, AL, United States of America"},{"name":"Institute of Health Sciences, Federal University of Jatai, Jatai, GO, 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America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tyler","family":"Beling","sequence":"additional","affiliation":[{"name":"Department of Physiology and Cell Biology, University of South Alabama, Mobile, AL, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Guerrero","sequence":"additional","affiliation":[{"name":"Department of Physiology and Cell Biology, University of South Alabama, Mobile, AL, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7115-1381","authenticated-orcid":false,"given":"Jaqueline","family":"Ho","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Pittsburgh, Pittsburgh, PA, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita de Cassia A","family":"Tostes","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Medical 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