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

• Published in: The Journal of steroid biochemistry and molecular biology Vol. 136; pp. 150 - 155
• Main Authors: Chen, Songcang, Gardner, David G.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.07.2013
• Subjects: Angiotensin II; Angiotensin II - administration & dosage; Animals; Cardiac hypertrophy; Ergocalciferols - pharmacology; Fibrosis; 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; Modulatory calcineurin inhibitor protein; Muscle Proteins - genetics; Myocardium - metabolism; Myocardium - pathology; Myocytes, Cardiac - metabolism; Myocytes, Cardiac - pathology; Paricalcitol; Receptors, Calcitriol - agonists; Receptors, Calcitriol - deficiency; Receptors, Calcitriol - metabolism; Vitamin D; Cardiac hypertrophy; Vitamin D; Angiotensin II; Modulatory calcineurin inhibitor protein; Fibrosis; Paricalcitol
• ISSN: 0960-0760; 1879-1220
• DOI: 10.1016/j.jsbmb.2012.09.007

▸ Liganded vitamin D receptor possesses potent anti-hypertrophic activity. ▸ The anti-hypertrophic activity displays in a non-renin-dependent model of cardiac hypertrophy. ▸ The anti-hypertrophic activity appears to involve suppression of the MCIP 1 protein. 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’.