MitoVasc Department, Team 2 (CarMe) and CARFI Facility, Angers University, F-49045 Angers, France.
Centre National de la Recherche Scientifique (CNRS), UMR 6015, F-49045 Angers, France.
Int J Mol Sci. 2022 Mar 5;23(5):2862. doi: 10.3390/ijms23052862.
Flow-mediated dilation (FMD) of resistance arteries is essential for tissue perfusion but it decreases with ageing. As estrogen receptor alpha (Erα encoded by ), and more precisely membrane ERα, plays an important role in FMD in young mice in a ligand-independent fashion, we evaluated its influence on this arteriolar function in ageing. We first confirmed that in young (6-month-old) mice, FMD of mesenteric resistance arteries was reduced in (lacking ERα) and C451A-ERα (lacking membrane ERα). In old (24-month-old) mice, FMD was reduced in WT mice compared to young mice, whereas it was not further decreased in and C451A-ERα mice. Markers of oxidative stress were similarly increased in old WT and C451A-ERα mice. Reduction in oxidative stress with superoxide dismutase plus catalase or Mito-tempo, which reduces mitochondrial superoxide restored FMD to a normal control level in young C451A-ERα mice as well as in old WT mice and old C451A-ERα mice. Estradiol-mediated dilation was absent in old WT mice. We conclude that oxidative stress is a key event in the decline of FMD, and that an early defect in membrane ERα recapitulates phenotypically and functionally ageing of these resistance arteries. The loss of this function could take part in vascular ageing.
血流介导的舒张（FMD）是抵抗动脉的基本功能，它随着年龄的增长而降低。因为雌激素受体α（由 编码），更确切地说是膜 ERα，在年轻小鼠中以非配体依赖的方式在 FMD 中发挥重要作用，所以我们评估了它对衰老过程中这种小动脉功能的影响。我们首先证实，在年轻（6 个月大）的小鼠中，肠系膜阻力动脉的 FMD 在 （缺乏 ERα）和 C451A-ERα（缺乏膜 ERα）中减少。在老年（24 个月大）的小鼠中，与年轻小鼠相比，WT 小鼠的 FMD 减少，而在 小鼠和 C451A-ERα 小鼠中则没有进一步减少。在 WT 和 C451A-ERα 老年小鼠中，氧化应激标志物也同样增加。超氧化物歧化酶加过氧化氢酶或 Mito-tempo 减少线粒体超氧化物，可将氧化应激减少恢复到年轻 C451A-ERα 小鼠以及老年 WT 小鼠和老年 C451A-ERα 小鼠的正常对照水平。在老年 WT 小鼠中，雌二醇介导的舒张不存在。我们得出结论，氧化应激是 FMD 下降的关键事件，而早期膜 ERα 缺陷重现了这些抵抗动脉的表型和功能衰老。这种功能的丧失可能参与了血管老化。
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