Transforming growth factor activity is a key determinant for the effect of estradiol on fatty streak deposit in hypercholesterolemic mice.

Abstract : OBJECTIVE: Whereas estradiol prevents fatty streak deposit in immunocompetent apoE-/- or LDLr-/- mice, it is totally ineffective in immunodeficient mice, underlining the key role of immunoinflammation in this effect. In the present work, the role of several major pro- and antiinflammatory cytokines involved in the atheromatous process was evaluated in the effect of estradiol on fatty streak constitution. METHODS AND RESULTS: The preventive effect of estradiol was fully maintained in LDLr-/- mice grafted with bone marrow from either IFN-gamma or interleukin (IL)-12-deficient mice, showing that this beneficial effect was not mediated through a specific decrease in the production of these 2 proinflammatory cytokines. Furthermore, IL-10-/- apoE-/- mice remained protected by estradiol, excluding a significant contribution of this antiinflammatory cytokine. In contrast, the protective effect of estradiol was (1) associated with enhanced aortic expression of TGF-beta1 in apoE-/- mice during early steps of atherogenesis; (2) abolished and even reversed in apoE-/- mice administered with a neutralizing anti-TGF-beta antibody; (3) abolished in LDLr-/- mice grafted with bone marrow from Smad3-deficient mice. CONCLUSIONS: The status of the TGF-beta pathway crucially determines the antiatherogenic effect of estradiol in hypercholesterolemic mice, whereas neither IFN-gamma, IL-12, nor IL-10 are specifically involved in this protection.
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Article dans une revue
Arteriosclerosis, Thrombosis, and Vascular Biology, American Heart Association, 2007, 27 (10), pp.2214-21. 〈10.1161/ATVBAHA.107.150300〉
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Soumis le : mardi 11 août 2009 - 11:26:25
Dernière modification le : lundi 24 août 2009 - 16:37:44

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Pierre Gourdy, Alexia Schambourg, Cédric Filipe, Victorine Douin-Echinard, Barbara Garmy-Susini, et al.. Transforming growth factor activity is a key determinant for the effect of estradiol on fatty streak deposit in hypercholesterolemic mice.. Arteriosclerosis, Thrombosis, and Vascular Biology, American Heart Association, 2007, 27 (10), pp.2214-21. 〈10.1161/ATVBAHA.107.150300〉. 〈inserm-00409639〉

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