1α,25-Dihydroxyvitamin D 3 and Its Potent Synthetic Analogs Downregulate Tissue Factor and Upregulate Thrombomodulin Expression in Monocytic Cells, Counteracting the Effects of Tumor Necrosis Factor and Oxidized LDL
- 5 December 2000
- journal article
- other
- Published by Wolters Kluwer Health in Circulation
- Vol. 102 (23) , 2867-2872
- https://doi.org/10.1161/01.cir.102.23.2867
Abstract
Background—We have recently found that a hormonally active form of vitamin D, 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3], exerts anticoagulant effects by upregulating the expression of an anticoagulant glycoprotein, thrombomodulin (TM), and downregulating the expression of a critical coagulation factor, tissue factor (TF), in monocytic cells including human peripheral monocytes. In this study, we investigated the counteracting effects of 1,25(OH)2D3 and its potent analogs on TF induction and TM downregulation by tumor necrosis factor and oxidized LDL in monocytic cells and the modulatory effects of potent analogs on TF and TM expression. Methods and Results—Effects of 1,25(OH)2D3 and its potent synthetic analogs (22R)-22-methyl-20-epi-1,25(OH)2D3 (KY3) and 22-oxacalcitriol on TF and TM antigen levels, cell surface activities, and mRNA levels in monocytic cells were examined. 1,25(OH)2D3 and its potent analogs showed anticoagulant effects in monocytic cells by downregulating TF and upregulating TM expression,...Keywords
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