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

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

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1
Diabetes Center, University of California at San Francisco, San Francisco, CA 94143-0540, United States. schen@diabetes.ucsf.edu

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'.

PMID:
22989481
DOI:
10.1016/j.jsbmb.2012.09.007
[Indexed for MEDLINE]
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