Estrogen resisted stress-induced cardiomyopathy through increasing the activity of β2AR-Gαs signal pathway in female rats
Estrogen resisted stress-induced cardiomyopathy through increasing the activity of β2AR-Gαs signal pathway in female rats
复制标题
雌激素通过增加雌性大鼠β(2)AR-G α s信号通路活性抵抗应激性心肌病
DOI：
10.1016/j.ijcard.2015.02.113
复制
发表时间：
2015-05-06
影响因子：
3.5
通讯作者：
Sun, Hong
中科院分区：
文献类型：
--
作者：
Cao, Xiancun;Zhou, Chunle;Sun, Hong
背景：应激性心肌病（SCM）的特征是短暂的左心室收缩功能障碍。90%以上的SCM患者为绝经后妇女，提示SCM的发生与雌激素水平低下有关。以往的研究表明，高水平的肾上腺素（epinephrine，EPI）通过将β 2肾上腺素受体（beta 2 adrenoceptor，β 2 AR）偶联由G α s信号通路转换为G α i信号通路而触发SCM。本研究旨在探讨雌激素是否通过调节β（2）AR-G蛋白信号通路来保护心肌免受SCM的侵害。方法：雌性SD大鼠随机分为假手术组（Sham）和去卵巢组（OVX）。卵巢切除后6周，血浆EPI和去甲肾上腺素水平显著升高。然后注射EPI制作SCM模型。雌激素缺乏导致急性EPI峰时心功能障碍更严重，心肌肌钙蛋白I（cTnI）浓度更高。用ICI 118，551预处理可消除卵巢切除引起的差异。克伦特罗预处理加重了Sham和OVX大鼠左心室血流动力学的差异。阻断G α i可消除高水平EPI对心肌细胞收缩的抑制作用。雌激素缺乏可降低OVX + EPI组cAMP含量和PKA磷酸化水平。注射EPI 20 min后，补充雌激素可增加EPI引起的OVX大鼠心肌cAMP浓度和PKA磷酸化水平。结论：雌激素可改善高水平EPI引起的心肌收缩抑制作用。雌激素通过增强β 2 AR-G α s信号通路的活性和降低血浆中儿茶酚胺的浓度来保护心肌免受SCM的损伤。(C)2015爱思唯尔爱尔兰有限公司版权所有。
Background: Stress-induced cardiomyopathy (SCM) is characterized by transient left ventricular systolic dysfunction. Over 90% of SCM patients are postmenopausal women, suggesting that the incidence of SCM is associated with low level of estrogen. Previous studies have shown that high levels of epinephrine (EPI) triggered SCM by switching beta(2)-adrenoceptor (beta(2)AR) coupling from G alpha s to G alpha i signaling pathway. This study examined whether estrogen protected myocardium against SCM through modulating the beta(2)AR-G proteins signal pathway.Methods and results: Female Sprague-Dawley (SD) rats were divided into sham operation (Sham) and ovariectomized (OVX) groups. Six weeks after ovariectomy, the plasma levels of EPI and norepinephrine significantly increased. Then they were injected with EPI to make SCM models. Lack of estrogen resulted in more serious cardiac dysfunction and higher cardiac troponin I (cTnI) concentration in acute EPI surge. Pretreatment with ICI118,551 abolished the discrepancy induced by ovariectomy. Pretreatment with clenbuterol aggravated the difference of left ventricular hemodynamics between Sham and OVX rats. Blocking G alpha i abolished the cardiomyocyte contractile inhibition by high levels of EPI. Estrogen deficiency decreased the concentration of cAMP and the phosphorylation of PKA in OVX + EPI group. After EPI injection for 20 min, acute estrogen supplementation could increase the concentration of cAMP and the phosphorylation of PKA in OVX rats suffered EPI-induced injury.Conclusions: Our results showed that estrogen improved the inhibitory effects of myocardial contraction induced by high levels of EPI. Estrogen protected myocardium against SCM via increasing the activity of beta(2)AR-G alpha s signal pathway and decreasing the concentration of catecholamine in plasma. (C) 2015 Elsevier Ireland Ltd. All rights reserved.