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dc.contributor.authorTorremadé Pascual, Noèlia
dc.contributor.authorBozić Stanojević, Milica
dc.contributor.authorPanizo García, Sara
dc.contributor.authorBarrio Vazquez, Sara
dc.contributor.authorFernandez Martín, José L.
dc.contributor.authorEncinas Martín, Mario
dc.contributor.authorGoltzman, David
dc.contributor.authorArcidiacono, Maria V.
dc.contributor.authorFernández i Giráldez, Elvira
dc.contributor.authorValdivielso Revilla, José Manuel
dc.date.accessioned2017-04-21T17:59:59Z
dc.date.available2017-04-21T17:59:59Z
dc.date.issued2016-04-01
dc.identifier.issn0884-0431
dc.identifier.urihttp://hdl.handle.net/10459.1/59526
dc.description.abstractVascular calcification (VC) is a complication of chronic kidney disease that predicts morbidity and mortality. Uremic serum promotes VC, but the mechanism involved is unknown. A role for 1,25(OH)2 D3 in VC has been proposed, but the mechanism is unclear because both low and high levels have been shown to increase it. In this work we investigate the role of 1,25(OH)2 D3 produced in vascular smooth muscle cells (VSMCs) in VC. Rats with subtotal nephrectomy and kidney recipient patients showed increased arterial expression of 1α-hydroxylase in vivo. VSMCs exposed in vitro to serum obtained from uremic rats also showed increased 1α-hydroxylase expression. Those increases were parallel to an increase in VC. After 6 days with high phosphate media, VSMCs overexpressing 1α-hydroxylase show significantly higher calcium content and RUNX2 expression than control cells. 1α-hydroxylase null mice (KO) with subtotal nephrectomy and treated with calcitriol (400 ng/kg) for 2 weeks showed significantly lower levels of vascular calcium content, Alizarin red staining, and RUNX2 expression than wild-type (WT) littermates. Serum calcium, phosphorus, blood urea nitrogen (BUN), PTH, and 1,25(OH)2 D3 levels were similar in both calcitriol-treated groups. In vitro, WT VSMCs treated with uremic serum also showed a significant increase in 1α-hydroxylase expression and higher calcification that was not observed in KO cells. We conclude that local activation of 1α-hydroxylase in the artery mediates VC observed in uremia. © 2016 American Society for Bone and Mineral Research.
dc.description.sponsorshipThis work was supported by a Grants form Instituto de Salud Carlos III (ISCIII)-FEDER funds (PI 12/01770, PI 11/00667, PI 14/00707), RedInRen (RD12/0021/0026 and RD12/0021/0023) and Plan de Ciencia, Tecnología e Innovación 2013-2017 del Principado de Asturias (GRUPIN14-028). N.T. is supported by studentship of IRBLleida and Universitat de Lleida. SBV is supported by FICYT (Severo Ochoa Program).
dc.format.mimetypeapplication/pdf
dc.language.isoeng
dc.publisherWiley
dc.relation.isformatofVersió postprint del document publicat a: https://doi.org/10.1002/jbmr.2852
dc.relation.ispartofJournal of Bone and Mineral Research, 2016, vol. 31, num. 10, p. 1865-1876
dc.rights(c) American Society for Bone and Mineral Research, 2016
dc.subject.classificationMalalties cardiovasculars
dc.subject.classificationMalalties del ronyó
dc.subject.classificationVitamina D
dc.subject.otherCardiovascular diseases
dc.subject.otherKidney diseases
dc.subject.otherVitamin D
dc.titleVascular calcification induced by chronic kidney disease is mediated by an increase of 1α-hydroxylase expression in vascular smooth muscle cells
dc.typeinfo:eu-repo/semantics/article
dc.date.updated2017-04-21T17:59:59Z
dc.identifier.idgrec024181
dc.type.versioninfo:eu-repo/semantics/acceptedVersion
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.identifier.doihttps://doi.org/10.1002/jbmr.2852


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