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Article Dans Une Revue Clinical Science Année : 2010

Countervailing vascular effects of rosiglitazone in high cardiovascular risk mice: Role of oxidative stress and PRMT-1

Carmine Savoia
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Talin Ebrahimian
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Catherine A Lemarié
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Pierre Paradis
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Marc Iglarz
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Farhad Amiri
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Danesh Javeshghani
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Ernesto L Schiffrin
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Résumé

We tested the hypothesis that the PPAR-γ activator rosiglitazone improves vascular structure and function in aged hyperhomocysteinemic methylene tetrahydrofolate reductase gene (MTHFR) heterozygous knockout mice (mthfr+/-) fed a high cholesterol diet (HCD), a model of high cardiovascular risk. One year-old mthfr+/- were fed or not HCD (6 mg/Kg/day) and treated or not with rosiglitazone (20 mg/Kg/day) for 90 days, and compared to wild-type mice. Endothelium dependent relaxation of carotid arteries was significantly impaired (-40%) only in rosiglitazone treated HCD-fed mthfr+/-. Carotid media-to-lumen ratio (M/L) and cross-sectional area (CSA) were increased (2-fold) in mthfr+/- fed or not HCD compared to wild-type mice (P<0.05). Rosiglitazone reduced M/L and CSA only in mthfr+/- fed a normal diet. Superoxide production was increased in mthfr+/- fed HCD treated or not with rosiglitazone, whereas plasma nitrite was reduced by rosiglitazone in mice fed or not HCD. Protein arginine methyltransferase-1 (PRMT-1), involved in synthesis of the NO synthase inhibitor asymmetric dimethylarginine (ADMA), and ADMA were increased only in rosiglitazone-treated HCD-fed mthfr+/-. Rosiglitazone had both beneficial and deleterious vascular effects in this animal model of high cardiovascular risk: it prevented carotid remodeling, but impaired endothelial function in part through enhanced oxidative stress and increased ADMA production in mice at high cardiovascular risk.

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Dates et versions

hal-00564472 , version 1 (09-02-2011)

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Carmine Savoia, Talin Ebrahimian, Catherine A Lemarié, Pierre Paradis, Marc Iglarz, et al.. Countervailing vascular effects of rosiglitazone in high cardiovascular risk mice: Role of oxidative stress and PRMT-1. Clinical Science, 2010, 118 (9), pp.583-592. ⟨10.1042/CS20090289⟩. ⟨hal-00564472⟩

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