Expression of the Vitamin D Receptor Is Increased in the Hypertrophic Heart

Hypertension. 2008 Dec;52(6):1106-12. doi: 10.1161/HYPERTENSIONAHA.108.119602. Epub 2008 Oct 20.

Abstract

The liganded vitamin D receptor (VDR) is thought to play an important role in controlling cardiac function. Specifically, this system has been implicated as playing an antihypertrophic role in the heart. Despite this, studies of VDR in the heart have been limited in number and scope. In the present study, we used a combination of real-time polymerase chain reaction, Western blot analysis, immunofluorescence, and transient transfection analysis to document the presence of functional VDR in both the myocytes and fibroblasts of the heart, as well as in the intact ventricular myocardium. We also demonstrated the presence of 1-alpha-hydroxylase and 24-hydroxylase in the heart, 2 enzymes involved in the synthesis and metabolism of 1,25 dihydroxyvitamin D. VDR is shown to interact directly with the human B-type natriuretic peptide gene promoter, a surrogate marker of the transcriptional response to hypertrophy. Of note, induction of myocyte hypertrophy either in vitro or in vivo leads to an increase in VDR mRNA and protein levels. Collectively, these findings suggest that the key components required for a functional 1,25 dihydroxyvitamin D-dependent signaling system are present in the heart and that this putatively antihypertrophic system is amplified in the setting of cardiac hypertrophy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cardiomegaly / metabolism*
  • Cardiomegaly / physiopathology*
  • Cells, Cultured
  • Fibroblasts / cytology
  • Fibroblasts / physiology
  • Gene Expression / physiology
  • Humans
  • Luciferases / genetics
  • Myocytes, Cardiac / cytology
  • Myocytes, Cardiac / physiology*
  • Natriuretic Peptide, Brain / genetics
  • Natriuretic Peptide, Brain / metabolism
  • Phosphatidylethanolamines
  • Rats
  • Rats, Sprague-Dawley
  • Rats, Wistar
  • Receptors, Calcitriol / genetics*
  • Receptors, Calcitriol / metabolism*
  • Signal Transduction / physiology
  • Vitamin D / analogs & derivatives
  • Vitamin D / metabolism

Substances

  • Phosphatidylethanolamines
  • Receptors, Calcitriol
  • Natriuretic Peptide, Brain
  • Vitamin D
  • transfectACE
  • 1,25-dihydroxyvitamin D
  • Luciferases