0343 : Importance of the membrane estrogen receptor alpha (ER) in the vascular response to shear stress in mice

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• 作者：Julie Favre¹ ; ^{julie.favre22@gmail.com" class="auth_mail" title="E-mail the corresponding author} ; Emilie Vessiè ; re¹ ; Anne-Laure Guihot¹ ; Linda Grimaud¹ ; Laurent Loufrani¹ ; Jean-Franç ; ois Arnal² ; Franç ; oise Lenfant² ; Daniel Henrion¹
• 刊名：Archives of Cardiovascular Diseases Supplements
• 出版年：2016
• 出版时间：April 2016
• 年：2016
• 卷：8
• 期：3
• 页码：216
• 全文大小：49 K

文摘

Resistance arteries are sensitive to mechanical forces exerted on the vessel wall. While endothelial shear stress triggers flow-mediated dilation (FMD), chronic increase in shear forces drives expansive arterial remodeling. We showed previously that endothelial estrogen receptor alpha (ER‹) controlled this adaptive remodeling. We aimed to evaluate ER‹contribution in acute response to flow, by using various genetic models of ER‹deficiency in male mice, reducing estrogen hormonal influence. FMD was evaluated following step increase in flow applied to pressurized mesenteric arteries (arteriography). Arteries were isolated from wild-type (WT), (i) ER‹KO, or mice invalidated for (ii) the ligand-dependent transactivation function AF2 of ERa (AF2°) and (iii) the plasma membrane-located ER‹(mutated for the palmitoylation site C451A). In mice deficient in ER‹, FMD was attenuated (dilation 50μl/min WT: 59+/–4% vs. ER‹KO: 41+/–4% p<0.01) without significant modification in response to acetylcholine. Invalidation of AF2 (ER‹nuclear transcriptional action) only partially impacted FMD (WT: 61+/–5% vs. AF2°: 51+/–5%). Ex vivo ligand-dependent activation of ER‹with 17®estradiol or blockade by ICI 182,780 had no significant effect on FMD in WT arteries. Importantly, invalidation of membrane ER‹(C451A) markedly altered FMD (WT: 56+/–7% vs. C451A: 34+/–6% p<0.05). In contrast to ER‹KO and AF2°, C451A arteries showed a reduced dilating response to acetylcholine but only a decreased sensitivity to insulin, which shares common intracellular pathways triggered by shear stress, without altering maximal vasodilation (WT: 31+/–7% vs. C451A: 15+/–3% p<0.05). We show for the first time that membrane ER‹contributes to arterial shear-sensing irrespective of the presence of its agonist. Cell membrane ER‹participates to vascular homeostasis and could constitute a novel therapeutical target in peripheral vascular diseases.

The author hereby declares no conflict of interest