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dc.contributor.authorDolcet Roca, Xavier
dc.contributor.authorEncinas Martín, Mario
dc.contributor.authorBozić Stanojević, Milica
dc.contributor.authorÁlvarez, Ángeles
dc.contributor.authorPablo, Carmen de
dc.contributor.authorSanchez-Niño, Maria-Dolores
dc.contributor.authorOrtiz, Alberto
dc.contributor.authorFernández i Giráldez, Elvira
dc.contributor.authorValdivielso Revilla, José Manuel
dc.description.abstractEndothelial cell activation leading to leukocyte recruitment and adhesion plays an essential role in the initiation and progression of atherosclerosis. Vitamin D has cardioprotective actions, while its deficiency is a risk factor for the progression of cardiovascular damage. Our aim was to assess the role of basal levels of vitamin D receptor (VDR) on the early leukocyte recruitment and related endothelial cell-adhesion-molecule expression, as essential prerequisites for the onset of atherosclerosis. Knockdown of VDR in endothelial cells (shVDR) led to endothelial cell activation, characterized by upregulation of VCAM-1, ICAM-1 and IL-6, decreased peripheral blood mononuclear cell (PBMC) rolling velocity and increased PBMC rolling flux and adhesion to the endothelium. shVDR cells showed decreased IκBα levels and accumulation of p65 in the nucleus compared to shRNA controls. Inhibition of NF-κB activation with super-repressor IκBα blunted all signs of endothelial cell activation caused by downregulation of VDR in endothelial cells. In vivo, deletion of VDR led to significantly larger aortic arch and aortic root lesions in apoE-/- mice, with higher macrophage content. apoE-/-VDR-/-mice showed higher aortic expression of VCAM-1, ICAM-1 and IL-6 when compared to apoE-/-VDR+/+ mice. Our data demonstrate that lack of VDR signaling in endothelial cells leads to a state of endothelial activation with increased leukocyte-endothelial cell interactions that may contribute to the more severe plaque accumulation observed in apoE-/-VDR-/- mice. The results reveal an important role for basal levels of endothelial VDR in limiting endothelial cell inflammation and atherosclerosis.ca_ES
dc.publisherPublic Library of Scienceca_ES
dc.relation.isformatofReproducció del document publicat a
dc.relation.ispartofPlos One, 2015, vol. 10, núm 8ca_ES
dc.rightscc-by (c) Valdivielso Revilla, José Manuel et al., 2015ca_ES
dc.titleImpaired Vitamin D Signaling in Endothelial Cell Leads to an Enhanced Leukocyte-Endothelium Interplay: Implications for Atherosclerosis Developmentca_ES

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cc-by (c) Valdivielso Revilla, José Manuel et al., 2015
Except where otherwise noted, this item's license is described as cc-by (c) Valdivielso Revilla, José Manuel et al., 2015