期刊
JOURNAL OF BONE AND MINERAL RESEARCH
卷 31, 期 10, 页码 1865-1876出版社
WILEY
DOI: 10.1002/jbmr.2852
关键词
CARDIOVASCULAR DISEASE; CHRONIC KIDNEY DISEASE; VITAMIN D; MINERAL METABOLISM; UREMIC TOXINS
资金
- Instituto de Salud Carlos III (ISCIII)-FEDER funds [PI 12/01770, PI 11/00667, PI 14/00707]
- RedInRen [RD12/0021/0026, RD12/0021/0023]
- Plan de Ciencia, Tecnologia e Innovacion del Principado de Asturias [GRUPIN14-028]
- IRBLleida
- Universitat de Lleida
- FICYT (Severo Ochoa Program)
Vascular calcification ( VC) is a complication of chronic kidney disease that predicts morbidity and mortality. Uremic serum promotes VC, but the mechanism involved is unknown. A role for 1,25( OH) D-2(3) in VC has been proposed, but the mechanism is unclear because both low and high levels have been shown to increase it. In this work we investigate the role of 1,25( OH) 2D3 produced in vascular smooth muscle cells ( VSMCs) in VC. Rats with subtotal nephrectomy and kidney recipient patients showed increased arterial expression of 1 alpha-hydroxylase in vivo. VSMCs exposed in vitro to serum obtained from uremic rats also showed increased 1 alpha-hydroxylase expression. Those increases were parallel to an increase in VC. After 6 days with high phosphate media, VSMCs overexpressing 1 alpha-hydroxylase show significantly higher calcium content and RUNX2 expression than control cells. 1 alpha-hydroxylase null mice ( KO) with subtotal nephrectomy and treated with calcitriol ( 400 ng/kg) for 2 weeks showed significantly lower levels of vascular calcium content, Alizarin red staining, and RUNX2 expression than wild-type ( WT) littermates. Serum calcium, phosphorus, blood urea nitrogen ( BUN), PTH, and 1,25( OH) 2D3 levels were similar in both calcitriol-treated groups. In vitro, WT VSMCs treated with uremic serum also showed a significant increase in 1 alpha-hydroxylase expression and higher calcification that was not observed in KO cells. We conclude that local activation of 1 alpha-hydroxylase in the artery mediates VC observed in uremia. (C) 2016 American Society for Bone and Mineral Research.
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