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Differential Effects of Vitamin D Receptor Agonists on Gene Expression in Neonatal Rat Cardiomyocytes

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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 (IC50 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.

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Abbreviations

VDR:

Vitamin D receptor

Aldo:

Aldosterone

CKD:

Chronic kidney disease

CYP27B1:

25-hydroxyvitamin D 1α-hydroxylase

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Acknowledgements

This work was supported by an investigator-initiated study grant from Abbott.

Conflict of interest

Drs. Wu-Wong, Chen and Nakane own Abbott stocks. Dr. Wolf has served as a consultant or received honoraria from Abbott, Amgen, Davita, Genzyme, Mitsubishi, Novartis and Shire.

This manuscript is original work not previously published in any substantial part, and is not under consideration of publication elsewhere. The manuscript has been read and approved for submission by all authors. The signature of the corresponding author is on behalf of all the authors.

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Authors and Affiliations

  1. University of Illinois at Chicago, 2201 W. Campbell Park Dr., Suite 13, Chicago, IL, 60612, USA

    J. Ruth Wu-Wong

  2. VidaGene, Chicago, IL, USA

    Yung-Wu Chen & Masaki Nakane

  3. University of Miami Miller School of Medicine, Miami, FL, USA

    Myles Wolf

Authors
  1. J. Ruth Wu-Wong
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  2. Yung-Wu Chen
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  3. Masaki Nakane
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Correspondence to J. Ruth Wu-Wong.

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Wu-Wong, J.R., Chen, YW., Nakane, M. et al. Differential Effects of Vitamin D Receptor Agonists on Gene Expression in Neonatal Rat Cardiomyocytes. Cardiovasc Drugs Ther 25, 215–222 (2011). https://doi.org/10.1007/s10557-011-6287-7

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