Estrogen inhibits the vascular injury response in estrogen receptor alpha-deficient mice
Estrogen inhibits the vascular injury response in estrogen receptor alpha-deficient mice
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DOI：
10.1038/nm0597-545
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发表时间：
1997-05-01
期刊：
影响因子：
82.9
通讯作者：
Mendelsohn, ME
中科院分区：
文献类型：
--
作者：
Iafrati, MD;Karas, RH;Mendelsohn, ME
雌激素对女性的动脉粥样硬化保护作用是公认的(1)，但其潜在的机制还不是很清楚。血管细胞表达经典的雌激素受体ERα(参考文献)。2-6)，并直接受到雌激素的影响，雌激素抑制动脉粥样硬化和损伤诱导的血管病变的发展(7，8)。我们已经产生了ERα基因被破坏的小鼠，并使用了颈动脉损伤的小鼠模型来比较雌激素对野生型和雌激素受体缺陷小鼠的影响。在卵巢切除的小鼠中，血管损伤后血管中层面积和平滑肌细胞增殖的增加被量化，用赋形剂或生理水平的17β-雌二醇处理。令人惊讶的是，在野生型和雌激素受体缺陷小鼠中，17β-雌二醇显著抑制所有血管损伤的措施，程度相同。这些数据表明，雌激素通过一种独立于经典雌激素受体ERα的新机制来抑制血管损伤。
The atheroprotective effects of estrogen in women are well recognized(1), but the underlying mechanisms responsible are not well understood. Blood vessel cells express the classic estrogen receptor, ER alpha (ref. 2-6), and are directly affected by estrogen, which inhibits the development of atherosclerotic and injury-induced vascular lesions(7,8). We have generated mice in which the ER alpha gene is disrupted(9) and have used a mouse model of carotid arterial injury to compare the effects of estrogen on wild-type and estrogen receptor-deficient mice. Increases in vascular medial area and smooth muscle cell proliferation were quantified following vascular injury in ovariectomized mice treated with vehicle or with physiologic levels of 17 beta-estradiol. Suprisingly, in both wild-type and estrogen receptor-deficient mice, 17 beta-estradiol markedly inhibited to the same degree all measures of vascular injury. These data demonstrate that estrogen inhibits vascular injury by a novel mechanism that is independent of the classic estrogen receptor, ER alpha.