Estrogen receptor alpha up-regulation and redistribution in human heart failure
Estrogen receptor alpha up-regulation and redistribution in human heart failure
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DOI：
10.1096/fj.05-5148com
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发表时间：
2006-05-01
期刊：
影响因子：
4.8
通讯作者：
Regitz-Zagrosek, Vera
中科院分区：
文献类型：
--
作者：
Mahmoodzadeh, Shokoufeh;Eder, Sarah;Regitz-Zagrosek, Vera
临床和动物研究表明，雌激素受体参与心肌肥厚和心力衰竭的发展。在这项研究中，我们研究了人类心肌雌激素受体α (ER α)的表达、定位以及与结构蛋白的关联是否在终末期心力衰竭中发生改变。我们发现，与对照组（n = 25）相比，终末期人类扩张型心肌病（DCM, n = 41）的ER α mRNA和蛋白增加了1.8倍。用共聚焦免疫荧光显微镜观察内质网α，内质网α定位于心肌细胞的细胞质、肌膜、间插盘和细胞核。免疫荧光研究证实了内质网α与β -连环蛋白在对照心脏嵌入盘的共定位，免疫沉淀研究证实了这两种蛋白的复合物形成。有趣的是，在DCM心脏中，内质网α / β -连环蛋白的共定位在嵌盘处丢失。因此，内质网α / β -连环蛋白在嵌入椎间盘中的共定位可能具有功能相关性，这种关联的丧失可能在心力衰竭的进展中起作用。总ER α表达的增加可能是一个代偿过程，有助于心脏间插盘的稳定性。
Clinical and animal studies suggest that estrogen receptors are involved in the development of myocardial hypertrophy and heart failure. In this study, we investigated whether human myocardial estrogen receptor alpha (ER alpha) expression, localization, and association with structural proteins was altered in end stage-failing hearts. We found a 1.8-fold increase in ER alpha mRNA and protein in end-stage human dilated cardiomyopathy ( DCM, n = 41), as compared with controls (n = 25). ER alpha was visualized by confocal immunofluorescence microscopy and localized to the cytoplasm, sarcolemma, intercalated discs and nuclei of cardiomyocytes. Immunofluorescence studies demonstrated colocalization of ER alpha with beta-catenin at the intercalated disc in control hearts and immunoprecipitation studies confirmed complex formation of both proteins. Interestingly, the ER alpha/beta-catenin colocalization was lost at the intercalated disc in DCM hearts. Thus, the ER alpha/beta-catenin colocalization in the intercalated disc may be of functional relevance and a loss of this association may play a role in the progression of heart failure. The increase of total ER alpha expression may represent a compensatory process to contribute to the stability of cardiac intercalated discs.