Chondro/osteoblastic and cardiovascular gene modulation in human artery smooth muscle cells that calcify in the presence of phosphate and calcitriol or paricalcitol

Vitamin D sterol administration, a traditional treatment for secondary hyperparathyroidism, may increase serum calcium and phosphorus, and has been associated with increased vascular calcification (VC). In vitro studies suggest that in the presence of uremic concentrations of phosphorus, vitamin D sterols regulate gene expression associated with trans‐differentiation of smooth muscle cells (SMCs) to a chondro/osteoblastic cell type. This study examined effects of vitamin D sterols on gene expression profiles associated with phosphate‐enhanced human coronary artery SMC (CASMC) calcification. Cultured CASMCs were exposed to phosphate‐containing differentiation medium (DM) with and without calcitriol, paricalcitol, or the calcimimetic R‐568 (10−11–10−7 M) for 7 days. Calcification of CASMCs, determined using colorimetry following acid extraction, was dose dependently increased (1.6‐ to 1.9‐fold) by vitamin D sterols + DM. In contrast, R‐568 did not increase calcification. Microarray analysis demonstrated that, compared with DM, calcitriol (10−8 M) + DM or paricalcitol (10−8 M) + DM similarly and significantly (P