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lüll 1,25-Dihydroxyvitamin D3-induced aortic calcifications in experimental uremia: up-regulation of osteoblast markers, calcium-transporting proteins and osterix Zebger-Gong H; Muller D; Diercke M; Haffner D; Hocher B; Verberckmoes S; Schmidt S; D'Haese PC; Querfeld UJ Hypertens 2011[Feb]; 29 (2): 339-48BACKGROUND AND OBJECTIVE: Whether treatment with vitamin D receptor activators contributes to cardiovascular disease in patients with chronic kidney disease is a matter of debate. We studied mechanisms involved in vitamin D-related vascular calcifications in vivo and in vitro. METHODS: Aortic calcifications were induced in subtotally nephrectomized (SNX) rats by treatment with a high dose (0.25 mug/kg per day) of 1,25-dihydroxyvitamin D3 (calcitriol) given for 6 weeks. Likewise, primary rat vascular smooth muscle cells (VSMCs) were incubated with calcitriol at concentrations ranging from 10 to 10 mol/l. Immunohistochemistry revealed that the aortic expression of osteopontin, osteocalcin and bone sialoprotein was significantly increased in calcitriol-treated SNX rats compared to untreated SNX controls. In addition, aortic expression of the transient receptor potential vanilloid calcium channel 6 (TRPV6) and calbindin D9k was significantly up-regulated by treatment with calcitriol. Furthermore, calcitriol significantly increased expression of the osteogenic transcription factor osterix. In-vitro studies showed similar results, confirming that these effects could be attributed to treatment with calcitriol. CONCLUSIONS: High-dose calcitriol treatment induces an osteoblastic phenotype in VSMC both in SNX rats and in vitro, associated with up-regulation of proteins regulating mineralization and calcium transport, and of the osteogenic transcription factor osterix.|Animals[MESH]|Aortic Diseases/*etiology/metabolism/pathology[MESH]|Base Sequence[MESH]|Biomarkers/metabolism[MESH]|Calbindins[MESH]|Calcinosis/*etiology/metabolism/pathology[MESH]|Calcitriol/administration & dosage/*adverse effects[MESH]|Calcium Channels/genetics/metabolism[MESH]|Calcium-Binding Proteins/genetics/metabolism[MESH]|Cells, Cultured[MESH]|Core Binding Factor Alpha 1 Subunit/genetics/metabolism[MESH]|DNA Primers/genetics[MESH]|Disease Models, Animal[MESH]|Humans[MESH]|Male[MESH]|Myocytes, Smooth Muscle/drug effects/metabolism[MESH]|Nephrectomy[MESH]|Osteoblasts/*drug effects/metabolism/pathology[MESH]|Rats[MESH]|Rats, Sprague-Dawley[MESH]|S100 Calcium Binding Protein G/genetics/metabolism[MESH]|TRPV Cation Channels/genetics/metabolism[MESH]|Transcription Factors/genetics/metabolism[MESH]|Up-Regulation/drug effects[MESH]|Uremia/*complications/metabolism/pathology[MESH] |