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Dietary Vitamin D and Its Metabolites Non-Genomically Stabilize the Endothelium.
Gibson, Christopher C; Davis, Chadwick T; Zhu, Weiquan; Bowman-Kirigin, Jay A; Walker, Ashley E; Tai, Zhengfu; Thomas, Kirk R; Donato, Anthony J; Lesniewski, Lisa A; Li, Dean Y.
Affiliation
  • Gibson CC; Program in Molecular Medicine, University of Utah, Salt Lake City, Utah, 84112, United States of America; Department of Bioengineering, University of Utah, Salt Lake City, Utah, 84112, United States of America; Recursion Pharmaceuticals, LLC, Salt Lake City, Utah, 84108, United States of America.
  • Davis CT; Program in Molecular Medicine, University of Utah, Salt Lake City, Utah, 84112, United States of America; Recursion Pharmaceuticals, LLC, Salt Lake City, Utah, 84108, United States of America; Department of Human Genetics, University of Utah, Salt Lake City, Utah, 84112, United States of America.
  • Zhu W; Program in Molecular Medicine, University of Utah, Salt Lake City, Utah, 84112, United States of America.
  • Bowman-Kirigin JA; Program in Molecular Medicine, University of Utah, Salt Lake City, Utah, 84112, United States of America.
  • Walker AE; Division of Geriatrics, Department of Medicine, University of Utah, Salt Lake City, Utah, 84112, United States of America.
  • Tai Z; The Key Laboratory for Human Disease Gene Study of Sichuan Province, Institute of Laboratory Medicine, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, Sichuan, 610072, China.
  • Thomas KR; Program in Molecular Medicine, University of Utah, Salt Lake City, Utah, 84112, United States of America; Recursion Pharmaceuticals, LLC, Salt Lake City, Utah, 84108, United States of America.
  • Donato AJ; Division of Geriatrics, Department of Medicine, University of Utah, Salt Lake City, Utah, 84112, United States of America.
  • Lesniewski LA; Division of Geriatrics, Department of Medicine, University of Utah, Salt Lake City, Utah, 84112, United States of America.
  • Li DY; Program in Molecular Medicine, University of Utah, Salt Lake City, Utah, 84112, United States of America; Recursion Pharmaceuticals, LLC, Salt Lake City, Utah, 84108, United States of America; Department of Human Genetics, University of Utah, Salt Lake City, Utah, 84112, United States of America; Th
PLoS One ; 10(10): e0140370, 2015.
Article in En | MEDLINE | ID: mdl-26469335
ABSTRACT
Vitamin D is a known modulator of inflammation. Native dietary vitamin D3 is thought to be bio-inactive, and beneficial vitamin D3 effects are thought to be largely mediated by the metabolite 1,25(OH)2D3. Reduced serum levels of the most commonly measured precursor metabolite, 25(OH)D3, is linked to an increased risk of multiple inflammatory diseases, including cardiovascular disease, arthritis, multiple sclerosis, and sepsis. Common to all of these diseases is the disruption of endothelial stability and an enhancement of vascular leak. We previously performed an unbiased chemical suppressor screen on a genetic model of vascular instability, and identified cholecalciferol (D3, dietary Vitamin D3) as a factor that had profound and immediate stabilizing and therapeutic effects in that model. In this manuscript we show that the presumed inactive sterol, D3, is actually a potent and general mediator of endothelial stability at physiologically relevant concentrations. We further demonstrate that this phenomenon is apparent in vitamin D3 metabolites 25(OH)D3 and 1,25(OH)2D3, and that the effects are independent of the canonical transcription-mediated vitamin D pathway. Our data suggests the presence of an alternative signaling modality by which D3 acts directly on endothelial cells to prevent vascular leak. The finding that D3 and its metabolites modulate endothelial stability may help explain the clinical correlations between low serum vitamin D levels and the many human diseases with well-described vascular dysfunction phenotypes.
Subject(s)

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Vitamins / Endothelium, Vascular / Cholecalciferol Type of study: Prognostic_studies Limits: Animals / Humans Language: En Journal: PLoS One Journal subject: CIENCIA / MEDICINA Year: 2015 Document type: Article Affiliation country: United States

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Vitamins / Endothelium, Vascular / Cholecalciferol Type of study: Prognostic_studies Limits: Animals / Humans Language: En Journal: PLoS One Journal subject: CIENCIA / MEDICINA Year: 2015 Document type: Article Affiliation country: United States