PMID- 22800987
OWN - NLM
STAT- MEDLINE
DCOM- 20130110
LR  - 20141120
IS  - 1879-1220 (Electronic)
IS  - 0960-0760 (Linking)
VI  - 132
IP  - 3-5
DP  - 2012 Nov
TI  - The vitamin D receptor activator paricalcitol prevents fibrosis and diastolic 
      dysfunction in a murine model of pressure overload.
PG  - 282-9
LID - S0960-0760(12)00124-0 [pii]
LID - 10.1016/j.jsbmb.2012.06.004 [doi]
AB  - BACKGROUND: Activation of the vitamin D-vitamin D receptor (VDR) axis has been 
      shown to reduce blood pressure and left ventricular (LV) hypertrophy. Besides 
      cardiac hypertrophy, cardiac fibrosis is a key element of adverse cardiac 
      remodeling. We hypothesized that activation of the VDR by paricalcitol would 
      prevent fibrosis and LV diastolic dysfunction in an established murine model of 
      cardiac remodeling. METHODS: Mice were subjected to transverse aortic 
      constriction (TAC) to induce cardiac hypertrophy. Mice were treated with 
      paricalcitol, losartan, or a combination of both for a period of four consecutive 
      weeks. RESULTS: The fixed aortic constriction caused similar increase in blood 
      pressure, both in untreated and paricalcitol- or losartan-treated mice. TAC 
      significantly increased LV weight compared to sham operated animals (10.2+/-0.7 vs. 
      6.9+/-0.3 mg/mm, p<0.05). Administration of either paricalcitol (10.5+/-0.7), 
      losartan (10.8+/-0.4), or a combination of both (9.2+/-0.6) did not reduce LV weight. 
      Fibrosis was significantly increased in mice undergoing TAC (5.9+/-1.0 vs. sham 
      2.4+/-0.8%, p<0.05). Treatment with losartan and paricalcitol reduced fibrosis 
      (paricalcitol 1.6+/-0.3% and losartan 2.9+/-0.6%, both p<0.05 vs. TAC). This 
      reduction in fibrosis in paricalcitol treated mice was associated with improved 
      indices of LV contraction and relaxation, e.g. dPdtmax and dPdtmin and lower LV 
      end diastolic pressure, and relaxation constant Tau. Also, treatment with 
      paricalcitol and losartan reduced mRNA expression of ANP, fibronectin, collagen 
      III and TIMP-1. DISCUSSION: Treatment with the selective VDR activator 
      paricalcitol reduces myocardial fibrosis and preserves diastolic LV function due 
      to pressure overload in a mouse model. This is associated with a reduced 
      percentage of fibrosis and a decreased expression of ANP and several other tissue 
      markers.
CI  - Copyright (c) 2012 Elsevier Ltd. All rights reserved.
FAU - Meems, Laura M G
AU  - Meems LM
AD  - Department of Cardiology, University of Groningen, University Medical Center 
      Groningen, P.O. Box 30.001, Postal code AB43, 9700 RB Groningen, The Netherlands.
FAU - Cannon, Megan V
AU  - Cannon MV
FAU - Mahmud, Hasan
AU  - Mahmud H
FAU - Voors, Adriaan A
AU  - Voors AA
FAU - van Gilst, Wiek H
AU  - van Gilst WH
FAU - Sillje, Herman H W
AU  - Sillje HH
FAU - Ruifrok, Willem P T
AU  - Ruifrok WP
FAU - de Boer, Rudolf A
AU  - de Boer RA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120716
PL  - England
TA  - J Steroid Biochem Mol Biol
JT  - The Journal of steroid biochemistry and molecular biology
JID - 9015483
RN  - 0 (Collagen Type III)
RN  - 0 (Ergocalciferols)
RN  - 0 (Fibronectins)
RN  - 0 (Tissue Inhibitor of Metalloproteinase-1)
RN  - 6702D36OG5 (paricalcitol)
RN  - 85637-73-6 (Atrial Natriuretic Factor)
RN  - JMS50MPO89 (Losartan)
SB  - IM
MH  - Animals
MH  - Aorta/drug effects
MH  - Atrial Natriuretic Factor/genetics
MH  - Blood Pressure/drug effects
MH  - Collagen Type III/genetics
MH  - Disease Models, Animal
MH  - Ergocalciferols/*pharmacology
MH  - Fibronectins/genetics
MH  - Fibrosis/prevention & control
MH  - Gene Expression Regulation/drug effects
MH  - Hypertrophy, Left Ventricular/*drug therapy/etiology/pathology
MH  - Losartan/pharmacology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Myocardium/pathology
MH  - Tissue Inhibitor of Metalloproteinase-1/genetics
MH  - Ventricular Function, Left/drug effects
MH  - Ventricular Pressure
MH  - Ventricular Remodeling/*drug effects
EDAT- 2012/07/18 06:00
MHDA- 2013/01/11 06:00
CRDT- 2012/07/18 06:00
PHST- 2012/02/15 00:00 [received]
PHST- 2012/06/21 00:00 [revised]
PHST- 2012/06/24 00:00 [accepted]
PHST- 2012/07/18 06:00 [entrez]
PHST- 2012/07/18 06:00 [pubmed]
PHST- 2013/01/11 06:00 [medline]
AID - S0960-0760(12)00124-0 [pii]
AID - 10.1016/j.jsbmb.2012.06.004 [doi]
PST - ppublish
SO  - J Steroid Biochem Mol Biol. 2012 Nov;132(3-5):282-9. doi: 
      10.1016/j.jsbmb.2012.06.004. Epub 2012 Jul 16.