17β-Estradiol promotes sex-specific dysfunction in isolated human arterioles.
17β-Estradiol promotes sex-specific dysfunction in isolated human arterioles.
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DOI：
10.1152/ajpheart.00708.2022
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发表时间：
2023-03-01
影响因子：
4.8
通讯作者：
Freed, Julie K.
中科院分区：
文献类型：
--
作者：
SenthilKumar, Gopika;Katunaric, Boran;Bordas-Murphy, Henry;Young, Micaela;Doren, Erin L.;Schulz, Mary E.;Widlansky, Michael E.;Freed, Julie K.
尽管数据显示雌激素在大导管动脉中具有血管保护作用，但绝经期激素治疗（HT）尚未被证明可以减轻心血管疾病（CVD）风险。通过长期口服避孕药和性别肯定疗法暴露于雌激素也会分别增加顺式和反式女性未来CVD的风险。微血管是一个独特的血管床，当功能障碍时，可以独立地预测未来的不良心脏事件;然而，雌激素对人体微血管的影响的研究是有限的。在这里，我们发现，在整个生命周期中，来自女性的分离的人小动脉维持一氧化氮（NO）介导的扩张以流动，而慢性（16-20小时）暴露于外源性（100 nM）17β-雌二醇促进年龄<40和≥40岁的成年女性血管中的微血管内皮功能障碍。雌激素的破坏作用在生物学男性的小动脉中更显着，因为它们表现出内皮和平滑肌功能障碍。此外，与≥40岁的女性和男性相比，<40岁的女性具有更高的雌激素受体-β（ER-β）和G蛋白偶联雌激素受体（GPER）的内皮表达。雌激素受体-α（ER-α）是与雌激素保护作用相关的主要受体，在所有组的外膜中而不是内皮中进行了鉴定。据我们所知，这是第一个研究报告的有害影响，雌激素对人类微血管和突出的差异，雌激素受体的表达。微血管功能障碍是不良心脏事件的独立预测因子;然而，雌激素对人体微循环的影响代表了一个关键的知识空白。据我们所知，这是第一个研究报告性别特异性有害影响的慢性雌激素对人类微血管反应。这些发现可能会提供洞察心血管疾病的风险增加与雌激素的使用在顺式和反式女性。
Despite data showing that estrogen is vasculoprotective in large conduit arteries, hormone therapy (HT) during menopause has not proven to mitigate cardiovascular disease (CVD) risk. Estrogen exposure through prolonged oral contraceptive use and gender-affirming therapy can also increase cis- and trans-females’ risk for future CVD, respectively. The microvasculature is a unique vascular bed that when dysfunctional can independently predict future adverse cardiac events; however, studies on the influence of estrogen on human microvessels are limited. Here, we show that isolated human arterioles from females across the life span maintain nitric oxide (NO)-mediated dilation to flow, whereas chronic (16–20 h) exposure to exogenous (100 nM) 17β-estradiol promotes microvascular endothelial dysfunction in vessels from adult females of <40 and ≥40 yr of age. The damaging effect of estrogen was more dramatic in arterioles from biological males, as they exhibited both endothelial and smooth muscle dysfunction. Furthermore, females of <40 yr have greater endothelial expression of estrogen receptor-β (ER-β) and G protein-coupled estrogen receptor (GPER) compared with females of ≥40 yr and males. Estrogen receptor-α (ER-α), the prominent receptor associated with protective effects of estrogen, was identified within the adventitia as opposed to the endothelium across all groups. To our knowledge, this is the first study to report the detrimental effects of estrogen on the human microvasculature and highlights differences in estrogen receptor expression. NEW & NOTEWORTHY Microvascular dysfunction is an independent predictor of adverse cardiac events; however, the effect of estrogen on the human microcirculation represents a critical knowledge gap. To our knowledge, this is the first study to report sex-specific detrimental effects of chronic estrogen on human microvascular reactivity. These findings may offer insight into the increased CVD risk associated with estrogen use in both cis- and trans-females.
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影响因子：
5.8
作者：
Moreau, Kerrie L.;Hildreth, Kerry L.;Kohrt, Wendy M.
通讯作者：
Kohrt, Wendy M.
影响因子：
3.7
作者：
Novensa, Laura;Novella, Susana;Dantas, Ana Paula
通讯作者：
Dantas, Ana Paula
影响因子：
--
作者：
KUO, L;DAVIS, MJ;CHILIAN, WM
通讯作者：
CHILIAN, WM
影响因子：
5
作者：
Thor D;Uchizono JA;Lin-Cereghino GP;Rahimian R
通讯作者：
Rahimian R
DOI：
10.1016/s0735-1097(97)00080-6
发表时间：
1997-06-01
影响因子：
24
作者：
New, G;Timmins, KL;Meredith, IT
通讯作者：
Meredith, IT