Differential effects of vitamin D receptor agonists on gene expression in neonatal rat cardiomyocytes

Purpose: Vitamin D receptor (VDR) activation is associated with cardiovascular benefits in chronic kidney disease patients, but whether VDR's hormone and prehormone exhibit similar effects requires more studies. Methods: Neonatal rat cardiomyocytes were treated with VDR agonists (calcitriol and/or paricalcitol) and the prehormone calcidiol in the presence of aldo (1 μM). The expression of VDR target genes were determined by real-time PCR and Western blotting. The expression and activity of CYP27B1 (the enzyme responsible for converting calcidiol to calcitriol) was measured. Results: Treating cells with aldo (1 μM) for 24 h significantly reduced the VDR mRNA (29%) and protein levels (>90%). Calcitriol and calcidiol induced VDR expression in the presence of aldo with EC₅₀ at 0.3 and 7,952 nM, respectively. Calcitriol, paricalcitol and calcidiol stimulated CYP24A1 (EC₅₀ at 6.4, 4.5 and 992 nM, respectively) and suppressed NPPB expression (IC ₅₀ at 1.9, 0.1 and 210 nM, respectively) in the presence of 1 μM aldo. Neonatal rat cardiomyocytes expressed CYP27B1 and converted calcidiol to calcitriol at a low rate (∼10% in 24 h). Conclusions: VDR hormone calcitriol and its analog paricalcitol exhibit more potent effects than the prehormone calcidiol in cardiomyocytes.