title: Liganded vitamin D receptor displays anti-hypertrophic activity in the murine heart.
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'.
authors.affiliation: Diabetes Center, University of California at San Francisco, San Francisco, CA 94143-0540, United States. schen@diabetes.ucsf.edu
authors.forename: Songcang
authors.initials: S
authors.lastname: Chen
authors.forename: David G
authors.initials: DG
authors.lastname: Gardner
mesh_terms: D000804:Angiotensin II / Q000008:administration & dosage; D000818:Animals; D002135:Calcium-Binding Proteins; D004872:Ergocalciferols / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D017379:Hypertrophy, Left Ventricular / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D008024:Ligands; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009124:Muscle Proteins / Q000235:genetics; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D018167:Receptors, Calcitriol / Q000819:agonists / Q000172:deficiency / Q000378:metabolism*
chemical_list: D002135:Calcium-Binding Proteins; C511512:DSCR1 protein, mouse; D004872:Ergocalciferols; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D009124:Muscle Proteins; D018167:Receptors, Calcitriol; D000804:Angiotensin II; C084656:paricalcitol