Vitamin D2 supplementation induces the development of aortic stenosis in rabbits : Interactions with endothelial function and thioredoxin-interacting protein

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Titre du document / Document title

Vitamin D₂ supplementation induces the development of aortic stenosis in rabbits : Interactions with endothelial function and thioredoxin-interacting protein

Auteur(s) / Author(s)

NGO Doan T. M.⁽¹⁾ ; STAFFORD Irene⁽¹⁾ ; KELLY Darren J.⁽²⁾ ; SVERDLOV Aaron L.⁽¹⁾ ; WUTTKE Ronald D.⁽¹⁾ ; WEEDON Helen⁽³⁾ ; NIGHTINGALE Angus K.⁽¹⁾ ; ROSENKRANZ Anke C.⁽¹⁾ ; SMITH Malcolm D.⁽³⁾ ; CHIRKOV Yuliy Y.⁽¹⁾ ; KENNEDY Jennifer A.⁽¹⁾ ; HOROWITZ John D.⁽¹⁾ ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

⁽¹⁾Cardiology Unit, The Queen Elizabeth Hospital, Department of Medicine, The University of Adelaide, AUSTRALIE
⁽²⁾Department of Medicine, St Vincent's Hospital, University of Melbourne, AUSTRALIE
⁽³⁾Rheumatology Unit, Repatriation Hospital, Flinders University, AUSTRALIE

Résumé / Abstract

Understanding of the pathophysiology of aortic valve stenosis (AVS) and finding potentially effective treatments are impeded by the lack of suitable AVS animal models. A previous study demonstrated the development of AVS in rabbits with vitamin D₂ and cholesterol supplementation without any hemodynamic changes in the cholesterol supplemented group alone. The current study aimed to determine whether AVS develops in an animal model with vitamin D₂ supplementation alone, and to explore pathophysiological mechanisms underlying this process. The effects of 8 weeks' treatment with vitamin D₂ alone (n=8) at 25,000 IU/4 days weekly on aortic valve structure and function were examined in male New Zealand white rabbits. Echocardiographic aortic valve backscatter (AV_BS), transvalvular velocity, and transvalvular pressure gradient were utilized to quantitate changes in valve structure and function. Valvular histology/ immunochemistry and function were examined after 8 weeks. Changes in valves were compared with those in endothelial function and in valvular measurement of thioredoxin-interacting protein (TXNIP), a marker/mediator of reactive oxygen species-induced oxidative stress. Vitamin D2 treated rabbits developed AVS with increased AV_BS (17.6±1.4 dB vs 6.7±0.8 dB, P<0.0001), increased transvalvular velocity and transvalvular pressure gradient (both P<0.01 via 2-way ANOVA) compared to the control group. There was associated valve calcification, lipid deposition and macrophage infiltration. Endothelial function was markedly impaired, and intravalvular TXNIP concentration increased. In this model, vitamin D₂ induces the development of AVS with histological features similar to those of early AVS in humans and associated endothelial dysfunction/ redox stress. AVS development may result from the loss of nitric oxide suppression of TXNIP expression.

Revue / Journal Title

European journal of pharmacology ISSN 0014-2999 CODEN EJPHAZ

Source / Source

2008, vol. 590, n^o1-3, pp. 290-296 [7 page(s) (article)] (3/4 p.)

Langue / Language

Anglais

Editeur / Publisher

Elsevier, Amsterdam, PAYS-BAS (1967) (Revue)

Localisation / Location

INIST-CNRS, Cote INIST : 13322, 35400019645804.0420

Nº notice refdoc (ud4) : 20558372