Estrogen rescues heart failure through estrogen receptor Beta activation.
Estrogen rescues heart failure through estrogen receptor Beta activation.
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DOI：
10.1186/s13293-018-0206-6
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发表时间：
2018-10-30
影响因子：
7.9
通讯作者：
Eghbali M
中科院分区：
文献类型：
--
作者：
Iorga A;Umar S;Ruffenach G;Aryan L;Li J;Sharma S;Motayagheni N;Nadadur RD;Bopassa JC;Eghbali M
最近，我们发现，外源性治疗雌激素（E2）挽救预先存在的先进的心力衰竭（HF）小鼠。由于E2的大多数生物学作用是通过经典的雌激素受体α（ERα）和/或β（ERβ）介导的，并且这两种受体都存在于心脏中，因此我们研究了ERα和ERβ在E2对HF的拯救作用中的作用。通过横向主动脉缩窄诱导的压力超负荷在雄性小鼠中诱导重度HF。一旦射血分数（EF）达到约35%，则用ERα（PPT，850 μg/kg/天）、ERβ（DPN，850 μ g/kg/天）或E2（30 μg/kg/天）的选择性激动剂与ERβ拮抗剂（PHTPP，850 μg/kg/天）联合给药小鼠10天。二芳基丙腈（DPN）治疗可使HF小鼠的EF显著提高至45.3 ± 2.1%，而PPT治疗则无此作用（31.1 ± 2.3%）。在存在PHTPP的情况下，E2未能挽救HF，因为在10天治疗结束时EF没有显著改善（32.5 ± 5.2%）。ERβ激动剂DPN治疗的HF小鼠心脏功能改善也与心脏纤维化减少和心脏血管生成增加有关，而ERα激动剂PPT对心脏纤维化或血管生成均无显著影响。此外，DPN改善HF小鼠的血流动力学参数，而PPT没有显着影响。E2治疗主要通过ERβ挽救既存重度HF。通过ERβ激活挽救HF还与刺激心脏血管生成、抑制纤维化和恢复血流动力学参数相关。
Recently, we showed that exogenous treatment with estrogen (E2) rescues pre-existing advanced heart failure (HF) in mice. Since most of the biological actions of E2 are mediated through the classical estrogen receptors alpha (ERα) and/or beta (ERβ), and both these receptors are present in the heart, we examined the role of ERα and ERβ in the rescue action of E2 against HF. Severe HF was induced in male mice by transverse aortic constriction-induced pressure overload. Once the ejection fraction (EF) reached ~ 35%, mice were treated with selective agonists for ERα (PPT, 850 μg/kg/day), ERβ (DPN, 850 μg/kg/day), or E2 (30 μg/kg/day) together with an ERβ-antagonist (PHTPP, 850 μg/kg/day) for 10 days. EF of HF mice was significantly improved to 45.3 ± 2.1% with diarylpropionitrile (DPN) treatment, but not with PPT (31.1 ± 2.3%). E2 failed to rescue HF in the presence of PHTPP, as there was no significant improvement in the EF at the end of the 10-day treatment (32.5 ± 5.2%). The improvement of heart function in HF mice treated with ERβ agonist DPN was also associated with reduced cardiac fibrosis and increased cardiac angiogenesis, while the ERα agonist PPT had no significant effect on either cardiac fibrosis or angiogenesis. Furthermore, DPN improved hemodynamic parameters in HF mice, whereas PPT had no significant effect. E2 treatment rescues pre-existing severe HF mainly through ERβ. Rescue of HF by ERβ activation is also associated with stimulation of cardiac angiogenesis, suppression of fibrosis, and restoration of hemodynamic parameters.
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DOI：
10.3969/j.issn.1671-5411.2013.04.008
发表时间：
2013-12
期刊：
Journal of geriatric cardiology : JGC
影响因子：
--
作者：
Barnabas O;Wang H;Gao XM
通讯作者：
Gao XM
影响因子：
9.3
作者：
Deschamps, Anne M.;Murphy, Elizabeth;Sun, Junhui
通讯作者：
Sun, Junhui
雌激素通过雌激素受体依赖性途径增加钙调神经素降解的途径。
影响因子：
20.1
作者：
Donaldson C;Eder S;Baker C;Aronovitz MJ;Weiss AD;Hall-Porter M;Wang F;Ackerman A;Karas RH;Molkentin JD;Patten RD
通讯作者：
Patten RD
影响因子：
37.8
作者：
Lin J;Steenbergen C;Murphy E;Sun J
通讯作者：
Sun J
DOI：
10.4172/2157-7013.1000153
发表时间：
2014-01-30
期刊：
Journal of cell science & therapy
影响因子：
--
作者：
Mahmoodzadeh S;Leber J;Zhang X;Jaisser F;Messaoudi S;Morano I;Furth PA;Dworatzek E;Regitz-Zagrosek V
通讯作者：
Regitz-Zagrosek V