Tie2-Cre-Induced Inactivation of Non-Nuclear Estrogen Receptor-α Signaling Abrogates Estrogen Protection Against Vascular Injury.
Tie2-Cre-Induced Inactivation of Non-Nuclear Estrogen Receptor-α Signaling Abrogates Estrogen Protection Against Vascular Injury.
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DOI：
10.1016/j.jacbts.2022.07.001
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发表时间：
2023-01
影响因子：
9.7
通讯作者：
Komuro, Issei
中科院分区：
文献类型：
--
作者：
Liu, Pang -Yen;Fukuma, Nobuaki;Hiroi, Yukio;Kunita, Akiko;Tokiwa, Hiroyuki;Ueda, Kazutaka;Kariya, Taro;Numata, Genri;Adachi, Yusuke;Tajima, Miyu;Toyoda, Masayuki;Li, Yuxin;Noma, Kensuke;Harada, Mutsuo;Toko, Haruhiro;Ushiku, Tetsuo;Kanai, Yoshimitsu;Takimoto, Eiki;Liao, James K.;Komuro, Issei
ERα上的Arg 263（人ERα的Arg 259）是参与与PI 3 K的p85α亚基相互作用的关键氨基酸，因此是非核信号传导。使用Cre-loxP系统，在具有完整核功能的内皮细胞中产生了ERα非核信号转导失活的新型小鼠模型。Tie 2-Cre诱导的ERα非核信号转导失活消除了雌激素对机械性血管损伤的保护作用，而对基线心血管和代谢表型的影响最小。使用Cre-loxP系统，我们产生了第一个小鼠模型，其中雌激素受体-α非核信号在内皮细胞中失活。雌激素对机械性血管损伤的保护作用在该模型中受损。这一结果表明，内皮雌激素受体-α非核信号在雌激素的血管保护作用中的关键作用。
Arg 263 on ERα (Arg 259 for human ERα) is a critical amino acid involved in the interaction with the p85α-subunit of PI3K and thus non-nuclear signaling. Using the Cre-loxP system, a novel mouse model in which ERα non-nuclear signaling was inactivated in endothelial cells with intact nuclear function was generated. Tie2-Cre–induced inactivation of ERα non-nuclear signaling abrogated the protection of estrogen against mechanical vascular injury, whereas it had a minimal impact on baseline cardiovascular and metabolic phenotypes. Using the Cre-loxP system, we generated the first mouse model in which estrogen receptor-α non-nuclear signaling was inactivated in endothelial cells. Estrogen protection against mechanical vascular injury was impaired in this model. This result indicates the pivotal role of endothelial estrogen receptor-α non-nuclear signaling in the vasculoprotective effects of estrogen.
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影响因子：
20.1
作者：
Garcia M;Mulvagh SL;Merz CN;Buring JE;Manson JE
通讯作者：
Manson JE
影响因子：
15.9
作者：
Chambliss, Ken L.;Wu, Qian;Shaul, Philip W.
通讯作者：
Shaul, Philip W.
影响因子：
4.5
作者：
Fleming, Ingrid
通讯作者：
Fleming, Ingrid
DOI：
10.1016/s0735-1097(01)01552-2
发表时间：
2001-11-01
影响因子：
24
作者：
Chandrasekar, B;Nattel, S;Tanguay, JF
通讯作者：
Tanguay, JF
影响因子：
7.7
作者：
Handgraaf, Sandra;Riant, Elodie;Gourdy, Pierre
通讯作者：
Gourdy, Pierre