Calcitriol Prevents In Vitro Vascular Smooth Muscle Cell Mineralization by Regulating Calcium-Sensing Receptor Expression

Vascular calcification (VC) is a degenerative disease that contributes to cardiovascular morbidity and mortality. A negative relationship has been demonstrated between VC and calcium sensing receptor (CaSR) expression in the vasculature. Of interest, vitamin D response elements, which allow responsiveness to 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], are present in the promoters of the CaSR gene. We hypothesized that 1,25(OH)2D3, by modulating CaSR expression in vascular smooth muscle cells (VSMCs), might protect against VC. Human VSMCs were exposed to increasing concentrations of 1,25(OH)2D3 (0.01–10 nmol/L) in noncalcifying (1.8 mmol/L) or procalcifying Ca2+0 condition (5.0 mmol/L). Using quantitative RT-PCR and Western blotting we observed a significant increase in both CaSR mRNA and protein levels after exposure to 1.0 nmol/L 1,25(OH)2D3. This effect was associated with a maximal increase in CaSR expression at the cell surface after 48 hours of 1,25(OH)2D3 treatment, as assessed by flow cytometry. Down-r...