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- Title
Vitamin D modulates tissue factor and protease-activated receptor 2 expression in vascular smooth muscle cells.
- Authors
Martinez-Moreno, Julio M.; Herencia, Carmen; de Oca, Addy Montes; Muñoz-Castañeda, Juan R.; Rodríguez-Ortiz, M. Encarnación; Díaz-Tocados, Juan M.; Peralbo-Santaella, Esther; Camargo, Antonio; Canalejo, Antonio; Rodriguez, Mariano; Velasco-Gimena, Francisco; Almaden, Yolanda
- Abstract
Clinical and epidemiologic studies reveal an association between vitamin D deficiency and increased risk of cardiovascular disease. Because vascular smooth muscle cell (VSMC)-derived tissue factor (TF) is suggested to be critical for arterial thrombosis, we investigated whether the vitamin D molecules calcitriol and paricalcitol could reduce the expression of TF induced by the proinflammatory cytokine TNF-a in human aortic VSMCs. We found that, compared with controls, incubation with TNF-a increased TF expression and procoagulant activity in a NF-B-dependent manner, as deduced from the increased nuclear translocation of nuclear factor -light-chain-enhancer of activated B cells protein 65 (p65-NF-B) and direct interaction of NF-B to the TF promoter. This was accompanied by the up-regulation of TF signaling mediator protease-activated receptor 2 (PAR-2) expression and by the down-regulation of vitamin D receptor expression in a miR-346-dependent way. However, addition of calcitriol or paricalcitol blunted the TNF-a-induced TF expression and activity (2.01 ± 0.24 and 1.32 ± 0.14 vs. 3.02 ± 0.39 pmol/mg protein, P < 0.05), which was associated with down-regulation of NF-B signaling and PAR-2 expression, as well as with restored levels of vitamin D receptor and enhanced expression of TF pathway inhibitor. Our data suggest that inflammation promotes a prothrombotic state through the up-regulation of TF function in VSMCs and that the beneficial cardiovascular effects of vitamin D may be partially due to decreases in TF expression and its activity in VSMCs.
- Subjects
VITAMIN D; THROMBOPLASTIN; PROTEASE-activated receptors; GENE expression; VASCULAR smooth muscle; MUSCLE cells
- Publication
FASEB Journal, 2016, Vol 30, Issue 3, p1367
- ISSN
0892-6638
- Publication type
Article
- DOI
10.1096/fj.15-272872