{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T05:03:04Z","timestamp":1789448584699,"version":"build-2803163510"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Endothelial dysfunction driven by intermittent hypoxia (IH)-induced oxidative stress, nitric oxide depletion, and adhesion molecule upregulation underlies obstructive sleep apnea (OSA)-related cardiovascular complications. Vitamin D deficiency, which frequently coexists with OSA, may further amplify this endothelial injury through impaired endothelial nitric oxide synthase (eNOS) regulation and heightened renin-angiotensin-aldosterone system (RAAS) activity; however, the dose-dependent therapeutic potential of vitamin D3 on combined endothelial and renal outcomes in an IH model remains uncharacterized.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Fifty-six adult male Sprague-Dawley rats were allocated to seven groups: control, vitamin D-deficient (VDD), VDD with severe IH (SIH-VDD), and four supplementation subgroups receiving high-dose (37.5\u00a0\u03bcg\/kg\/day) or low-dose (25\u00a0\u03bcg\/kg\/day) cholecalciferol under severe or moderate IH for 14 days. Serum E-selectin, ICAM-1, ET-1, NO, and PCSK9 were quantified by ELISA. Renal histopathology was assessed on H&amp;amp;E sections by a blinded pathologist. Data were analyzed by one-way MANOVA, univariate ANOVA, and LSD\n                      <jats:italic>post hoc<\/jats:italic>\n                      tests (p &amp;lt; 0.05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The SIH-VDD group showed the most severe endothelial activation: peak E-selectin (4.92 \u00b1 0.90\u00a0ng\/mL), ICAM-1 (201.50 \u00b1 21.55\u00a0ng\/mL), ET-1 (5.31 \u00b1 0.81\u00a0pg\/mL), and PCSK9 (213.50 \u00b1 14.71\u00a0ng\/mL), with the lowest NO (14.88 \u00b1 2.16\u00a0\u03bcmol\/L; all p &amp;lt; 0.001 vs. control). High-dose supplementation produced substantial recovery across all markers; PCSK9 normalized to near-control (162.50\u00a0ng\/mL) under severe IH. Low-dose supplementation yielded incomplete normalization. Renal histopathology revealed mild interstitial lymphocytic infiltration in IH-exposed groups, with proximal tubular vacuolisation exclusively in the SIH-VDD group and entirely absent in all supplemented groups. Glomerular architecture remained preserved throughout.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Vitamin D deficiency combined with IH upregulates endothelial dysfunction markers and induces renal tubular injury in an experimental OSA model. High-dose vitamin D\n                      <jats:sub>3<\/jats:sub>\n                      attenuates these changes dose- and severity-dependently, supporting its role as a pharmacological adjunct for OSA-associated endothelial and renal complications.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1847011","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T04:28:00Z","timestamp":1789446480000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Dose-dependent vitamin D3 supplementation attenuates endothelial dysfunction and renal injury in an obstructive sleep apnea rat model"],"prefix":"10.3389","volume":"17","author":[{"given":"Abdulmueen A.","family":"Alotaibi","sequence":"first","affiliation":[{"name":"Department of Physiology, College of Medicine, King Saud University","place":["Riyadh, Saudi Arabia"]},{"name":"Anesthesia Technology Department, Almaarefa University College of Applied Sciences","place":["Riyadh, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Syed Shahid","family":"Habib","sequence":"additional","affiliation":[{"name":"Department of Physiology, College of Medicine, King Saud University","place":["Riyadh, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hayam","family":"Gad","sequence":"additional","affiliation":[{"name":"Department of Physiology, College of Medicine, King Saud University","place":["Riyadh, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamadar","family":"Al Doheyan","sequence":"additional","affiliation":[{"name":"Department of Pathology, College of Medicine, King Khalid University Hospital, King Saud University","place":["Riyadh, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mubarak","family":"Aldosary","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Care, Ministry of National Guard Health Affairs","place":["Riyadh, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alanoud T.","family":"Aljasham","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University","place":["Riyadh, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asma F.","family":"Alotaibi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University","place":["Riyadh, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasser A.","family":"Alshawakir","sequence":"additional","affiliation":[{"name":"Experimental Surgery and Animal Laboratory, Prince Naif bin Abdulaziz Health Research Center (PNHRC), College of Medicine, King Saud University","place":["Riyadh, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuzail","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Respiratory Therapy Department, Almaarefa University College of Applied Sciences","place":["Riyadh, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abeer A.","family":"Al-Masri","sequence":"additional","affiliation":[{"name":"Department of Physiology, College of Medicine, King Saud University","place":["Riyadh, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e0192084","DOI":"10.1371\/journal.pone.0192084","article-title":"Intermittent hypoxia causes histological kidney damage and increases growth factor expression in a mouse model of obstructive sleep apnea","volume":"13","author":"Abuyassin","year":"2018","journal-title":"PLOS ONE"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1542898","DOI":"10.3389\/FMOLB.2025.1542898","article-title":"Development of an ELISA for determining neutrophil elastase, a potential marker of multi-organ damage in COVID-19","volume":"12","author":"Adamiec-Mroczek","year":"2025","journal-title":"Front. 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