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

J. Ruth Wu-Wong, Yung Wu Chen, Masaki Nakane, Myles Wolf

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)215-222
Number of pages8
JournalCardiovascular Drugs and Therapy
Volume25
Issue number3
DOIs
StatePublished - Jun 1 2011

Keywords

  • Calcidiol
  • Calcitriol
  • Cardiomyocytes
  • Paricalcitol
  • Vitamin D receptor

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine
  • Pharmacology (medical)

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