RT Journal Article SR Electronic T1 Role of Phosphorus and Vitamin D Analogs in the Pathogenesis of Vascular Calcification JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP 90 OP 98 DO 10.1124/jpet.106.101261 VO 318 IS 1 A1 J. Ruth Wu-Wong A1 William Noonan A1 Junli Ma A1 Doug Dixon A1 Masaki Nakane A1 Antoinette L. Bolin A1 Kristin A. Koch A1 Steve Postl A1 Sherry J. Morgan A1 Glenn A. Reinhart YR 2006 UL http://jpet.aspetjournals.org/content/318/1/90.abstract AB Vascular calcification is a mortality risk factor for stage 5 chronic kidney disease patients. We investigated the role of phosphorus and vitamin D analogs in the pathogenesis of vascular calcification using in vivo, ex vivo, and in vitro models. Our results demonstrate that uremic rats receiving a hyperphosphatemia-inducing diet did not exhibit aortic calcification despite elevated levels of serum phosphorus and calcium-phosphorus (CaxP) product. The vitamin D analog 1α-hydroxyvitamin-D2 [1α(OH)D2] at 0.17 μg/kg raised serum calcium, phosphorus, CaxP product, and aortic calcification in the uremic rats, but 19-nor-1α,25(OH)2D2 (19-nor) at the same dose had no significant effect. At 0.67 μg/kg, both 1α(OH)D2 and 19-nor had similar effects on serum calcium, phosphorus, and CaxP product, but only 1α(OH)D2 induced significant aortic calcification. Only aortic rings from 1α(OH)D2-treated uremic rats exhibited a significant increase in 45Ca uptake ex vivo. When aortic rings from normal rats or a primary culture of human coronary artery smooth muscle cells were treated with phosphorus or vitamin D analogs in vitro, high phosphorus induced calcium accumulation and/or 45Ca uptake in a dose- or time-dependent manner, whereas vitamin D analogs including 1α(OH)D2 up to 100 nM had no significant effect despite the presence of a functional vitamin D receptor. However, serum from 1α(OH)D2-treated uremic rats induced 45Ca uptake into smooth muscle cells cultured in high phosphorus. These results suggest that the regulation of vascular calcification in vivo cannot be easily replicated in the ex vivo or in vitro models, and high phosphorus and some vitamin D analogs such as 1α(OH)D2 exert interactive effects on modulating vascular calcification. The American Society for Pharmacology and Experimental Therapeutics