TY  - JOUR
A1  - Zebger-Gong, Hong
A1  - Mueller, Dominik
A1  - Diercke, Michaela
A1  - Haffner, Dieter
A1  - Hocher, Berthold
A1  - Verberckmoes, Steven
A1  - Schmidt, Sven
A1  - D'Haese, Patrick C.
A1  - Querfeld, Uwe
T1  - 1,25-Dihydroxyvitamin D-3-induced aortic calcifications in experimental uremia: up-regulation of osteoblast markers, calcium-transporting proteins and osterix
JF  - Journal of hypertension
N2  - Background 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 mu g/kg per day) of 1,25-dihydroxyvitamin D-3 (calcitriol) given for 6 weeks. Likewise, primary rat vascular smooth muscle cells (VSMCs) were incubated with calcitriol at concentrations ranging from 10(-11) to 10(-7) 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.
KW  - calbindin D9k
KW  - calcitriol
KW  - calcium transport
KW  - osteoblast
KW  - osterix
KW  - TRPV5
KW  - TRPV6
KW  - vascular calcification
Y1  - 2011
U6  - https://doi.org/10.1097/HJH.0b013e328340aa30
SN  - 0263-6352
VL  - 29
IS  - 2
SP  - 339
EP  - 348
PB  - Lippincott Williams & Wilkins
CY  - Philadelphia
ER  -