Tamoxifen elicits atheroprotection through estrogen receptor α AF-1 but does not accelerate reendothelialization. - Université de Rennes Accéder directement au contenu
Article Dans Une Revue American Journal of Pathology Année : 2013

Tamoxifen elicits atheroprotection through estrogen receptor α AF-1 but does not accelerate reendothelialization.

Résumé

Based on both experimental and clinical data, tamoxifen has been proposed to have cardiovascular benefits, although the mechanism(s) contributing to that protective effect are still poorly understood. In vitro experiments demonstrated that tamoxifen elicits its transcriptional effect through estrogen receptor (ER) α, but other targets can participate in its actions. However, although tamoxifen selectively activates the activating function (AF)-1 of ERα, we recently showed that this ERα subfunction is dispensable for the atheroprotective action of 17β-estradiol (E2), the main ligand of ERs. The goal of the present work is to determine to which extent ERα and its AF-1 mediate the vasculoprotective action of tamoxifen. Our data confirm that tamoxifen exerts an atheroprotective action on low density lipoprotein receptor (LDL-r(-/-)) female mice, but, in contrast to E2, it fails to accelerate reendothelialization after carotid electric injury. Tamoxifen and E2 elicit differences in gene expression profiles in the mouse aorta. Finally, the atheroprotective action of tamoxifen is abrogated in ERα(-/-)LDL-r(-/-) mice and in LDL-r(-/-) mice selectively deficient in ERαAF-1 (ERαAF-1(0/0)LDL-r(-/-)). Our results demonstrate, for the first time to our knowledge, that tamoxifen mediates its actions in vivo through the selective activation of ERαAF-1, which is sufficient to prevent atheroma, but not to accelerate endothelial healing.

Dates et versions

hal-00874317 , version 1 (17-10-2013)

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Coralie Fontaine, Anne Abot, Audrey Billon-Galés, Gilles Flouriot, Hortense Bergès, et al.. Tamoxifen elicits atheroprotection through estrogen receptor α AF-1 but does not accelerate reendothelialization.. American Journal of Pathology, 2013, 183 (1), pp.304-12. ⟨10.1016/j.ajpath.2013.03.010⟩. ⟨hal-00874317⟩
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