Attenuation of Atherogenesis via the Anti-inflammatory Effects of the Selective Estrogen Receptor Beta Modulator 8β-VE2
Attenuation of Atherogenesis via the Anti-inflammatory Effects of the Selective Estrogen Receptor Beta Modulator 8β-VE2
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通过选择性雌激素受体 β 调节剂 8β-VE2 的抗炎作用减弱动脉粥样硬化形成
DOI：
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发表时间：
2011
影响因子：
3
通讯作者：
E. O’Brien
中科院分区：
文献类型：
--
作者：
Jiangfeng Sun;Xiaoli Ma;Yong;K. Rayner;B. Hibbert;M. McNulty;B. Dhaliwal;T. Simard;D. Ramirez;E. O’Brien
背景：最近的研究表明，雌激素受体β (ERβ)的调节可能在维持血管稳态中起着至关重要的作用。我们假设选择性的ERβ激活会通过抗炎机制减弱动脉粥样硬化的发生。方法和结果：易发生动脉粥样硬化的apoE - / -小鼠切除卵巢，饲喂高胆固醇饮食，每天皮下注射高选择性强效ERβ激动剂（8β-VE2），持续5周。与对照组相比，8β-VE2治疗使主动脉弓动脉粥样硬化病变面积减少了总面积的34%，致密病变面积减少了75%，而血脂水平没有改变。我们将这些观察到的血管作用完全归因于ERβ调节，因为(1)使用非选择性ER拮抗剂ICI 182780完全消除了8β-VE2的有益血管作用，(2)子宫重量（ERα调节的敏感指标）没有随8β-VE2治疗而改变。此外，8β-VE2处理小鼠血清白细胞介素1β和肿瘤坏死因子α水平降低。最后，用8β-VE2体外处理巨噬细胞阻断乙酰化低密度脂蛋白的摄取，抑制炎症细胞因子肿瘤坏死因子α的细胞外水平，提高抗动脉粥样硬化/抗炎蛋白热休克蛋白27的细胞外水平。结论：8β-VE2选择性激活ERβ可减轻动脉粥样硬化的发生，并与血管炎症的有利调节有关。
Background: Recent studies suggest that modulation of estrogen receptor β (ERβ) may play a crucial role in maintaining vascular homeostasis. We hypothesized that selective ERβ activation will attenuate atherogenesis via anti-inflammatory mechanisms. Methods and Results: Atherosclerosis-prone apoE−/− mice were ovariectomized and then fed a high-cholesterol diet with daily subcutaneous injections of the highly selective and potent ERβ agonist (8β-VE2) for 5 weeks. Compared with controls, treatment with 8β-VE2 reduced aortic arch atherosclerotic lesion areas by 34% of total and 75% of dense lesions, while not altering the serum lipid profile. We attribute these observed vascular effects solely to ERβ modulation as (1) treatment with the nonselective ER antagonist ICI 182,780 completely abrogated the beneficial vascular effects of 8β-VE2 and (2) uterine weight (a sensitive indicator of ERα modulation) did not change with 8β-VE2 treatment. Moreover, mice treated with 8β-VE2 had reduced serum interleukin 1β and tumor necrosis factor α levels. Finally, treatment of macrophages in vitro with 8β-VE2 blocked the uptake of acetylated low-density lipoprotein, suppressed the extracellular levels of the inflammatory cytokine tumor necrosis factor α, and enhanced the extracellular levels of the antiatherogenic/anti-inflammatory protein heat shock protein 27. Conclusions: Selective ERβ activation by 8β-VE2 attenuates atherogenesis and is associated with favorable modulation of vascular inflammation.
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影响因子：
20.1
作者：
Lindner, V;Kim, SK;Mendelsohn, ME
通讯作者：
Mendelsohn, ME
影响因子：
4.8
作者：
Burke, AP;Farb, A;Virmani, R
通讯作者：
Virmani, R
DOI：
10.1152/ajpregu.00373.2006
发表时间：
2007-02-01
影响因子：
2.8
作者：
Rayner, Katey;Chen, Yong-Xiang;O'Brien, Edward R.
通讯作者：
O'Brien, Edward R.
DOI：
10.1016/s0002-9149(02)02405-0
发表时间：
2002-06
期刊：
The New England journal of medicine
影响因子：
--
作者：
M. Mendelsohn;R. Karas
通讯作者：
M. Mendelsohn;R. Karas
影响因子：
9.3
作者：
Rexrode, Kathryn M.;Ridker, Paul M.;Zee, Robert Y. L.
通讯作者：
Zee, Robert Y. L.