Transforming growth factor activity is a key determinant for the effect of estradiol on fatty streak deposit in hypercholesterolemic mice.
Arterioscler Thromb Vasc Biol
; 27(10): 2214-21, 2007 Oct.
Article
em En
| MEDLINE
| ID: mdl-17690314
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 ANDRESULTS:
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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Base de dados:
MEDLINE
Assunto principal:
Aorta
/
Estradiol
/
Aterosclerose
/
Fator de Crescimento Transformador beta1
/
Hipercolesterolemia
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
Idioma:
En
Revista:
Arterioscler Thromb Vasc Biol
Assunto da revista:
ANGIOLOGIA
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
França