Effect of paricalcitol and calcitriol on aortic wall remodeling in uninephrectomized ApoE knockout mice
Contribuinte(s) |
UNIVERSIDADE DE SÃO PAULO |
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Data(s) |
19/10/2012
19/10/2012
2011
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Resumo |
Becker LE, Koleganova N, Piecha G, Noronha IL, Zeier M, Geldyyev A, Kokeny G, Ritz E, Gross ML. Effect of paricalcitol and calcitriol on aortic wall remodeling in uninephrectomized ApoE knockout mice. Am J Physiol Renal Physiol 300: F772-F782, 2011. First published December 15, 2010; doi:10.1152/ajprenal.00042.2010.-Despitean only minor reduction in the glomerular filtration rate, uninephrectomy (UNX) markedly accelerates the rate of growth of atherosclerotic plaques in ApoE-/- mice. It has been suggested that vitamin D receptor (VDR) activation exerts an antiproliferative effect on vascular smooth muscle cells, but the side effects may limit its use. To assess a potentially different spectrum of actions, we compared the effects of paricalcitol and calcitriol on remodeling and calcification of the aortic wall in sham-operated and UNX ApoE-/- mice on a diet with normal cholesterol content. Sham-operated and UNX mice were randomly allotted to treatment with solvent, calcitriol (0.03 mu g/kg) or paricalcitol (0.1 mu g/kg) 5 times/wk intraperitoneally for 10 wk. Semithin (0.6 mu m) sections of the aorta were analyzed by 1) morphometry, 2) immunohistochemistry, and 3) Western blotting of key proteins involved in vascular calcification and growth. Compared with sham-operated animals (5.6 +/- 0.24), the wall-to-lumen ratio (x100) of the aorta was significantly higher in solvent-and calcitriol-treated UNX animals (6.64 +/- 0.27 and 7.17 +/- 0.81, respectively, P < 0.05), but not in paricalcitol-treated UNX (6.1 5 +/- 0.32). Similar differences were seen with respect to maximal plaque height. Expression of transforming growth factor (TGF)-beta 1 in aortic intima/plaque was also significantly higher in UNX solvent and UNX calcitriol compared with sham-operated and UNX paricalcitol animals. Treatment with both paricalcitol and calcitriol caused significant elevation of VDR expression in the aorta. While at the dose employed paricalcitol significantly reduced TGF-beta expression in plaques, calcitriol in contrast caused significant vascular calcification and elevated expression of related proteins (BMP2, RANKL, and Runx2). CAPES/DAAD Abbott Laboratories, Chicago, IL |
Identificador |
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, v.300, n.3, p.F772-F782, 2011 1931-857X http://producao.usp.br/handle/BDPI/21683 10.1152/ajprenal.00042.2010 |
Idioma(s) |
eng |
Publicador |
AMER PHYSIOLOGICAL SOC |
Relação |
American Journal of Physiology-renal Physiology |
Direitos |
restrictedAccess Copyright AMER PHYSIOLOGICAL SOC |
Palavras-Chave | #vitamin D/analogs and derivates #atherosclerosis #vascular calcification #uninephrectomy #ApoE-/- #SOFT-TISSUE CALCIFICATION #CHRONIC KIDNEY-DISEASE #SMOOTH-MUSCLE-CELLS #VITAMIN-D ANALOGS #VASCULAR CALCIFICATION #COMBINATION THERAPY #MORTALITY RISK #HEMODIALYSIS #ATHEROGENESIS #PROGRESSION #Physiology #Urology & Nephrology |
Tipo |
article original article publishedVersion |