Liganded vitamin D receptor displays anti-hypertrophic activity in the murine heart

J Steroid Biochem Mol Biol. 2013 Jul:136:150-5. doi: 10.1016/j.jsbmb.2012.09.007. Epub 2012 Sep 16.

Abstract

Vitamin D and its analogs have been suggested to have palliative effects in the cardiovascular system. We have examined the effects of co-administration of the vitamin D receptor agonist, paricalcitol, on the hypertension, cardiac hypertrophy and interstitial fibrosis produced by chronic angiotensin II (AII) infusion. Administration of AII (800ng/kg/min) over a 14-day period resulted in increased blood pressure, myocyte hypertrophy, activation of the hypertrophic fetal gene program (atrial natriuretic peptide, B-type natriuretic peptide and alpha skeletal actin gene expression), increased expression of the pro-hypertrophic modulatory calcineurin inhibitor protein 1 (MCIP 1), and increased fibrosis with augmented procollagen 1 and 3 gene expression. In each case co-administration of paricalcitol (300ng/kg intraperitoneally every 48h) at least partially reversed the AII-dependent effect. These studies demonstrate that the liganded vitamin D receptor possesses potent anti-hypertrophic activity in this non-renin-dependent model of cardiac hypertrophy. The anti-hypertrophic activity appears to be at least partially intrinsic to the cardiac myocyte and may involve suppression of the MCIP 1 protein. This article is part of a Special Issue entitled 'Vitamin D Workshop'.

Publication types

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

MeSH terms

  • Angiotensin II / administration & dosage
  • Animals
  • Calcium-Binding Proteins
  • Ergocalciferols / pharmacology
  • Gene Expression / drug effects
  • Hypertrophy, Left Ventricular / metabolism*
  • Hypertrophy, Left Ventricular / pathology
  • Hypertrophy, Left Ventricular / prevention & control*
  • Intracellular Signaling Peptides and Proteins / genetics
  • Ligands
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Muscle Proteins / genetics
  • Myocardium / metabolism*
  • Myocardium / pathology
  • Myocytes, Cardiac / metabolism
  • Myocytes, Cardiac / pathology
  • Receptors, Calcitriol / agonists
  • Receptors, Calcitriol / deficiency
  • Receptors, Calcitriol / metabolism*

Substances

  • Calcium-Binding Proteins
  • DSCR1 protein, mouse
  • Ergocalciferols
  • Intracellular Signaling Peptides and Proteins
  • Ligands
  • Muscle Proteins
  • Receptors, Calcitriol
  • Angiotensin II
  • paricalcitol