Alteration of β-Adrenoceptor Signaling in Left Ventricle of Acute Phase Takotsubo Syndrome: a Human Study.
Alteration of β-Adrenoceptor Signaling in Left Ventricle of Acute Phase Takotsubo Syndrome: a Human Study.
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DOI：
10.1038/s41598-018-31034-z
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发表时间：
2018-08-24
影响因子：
4.6
通讯作者：
Saito Y
中科院分区：
文献类型：
--
作者：
Nakano T;Onoue K;Nakada Y;Nakagawa H;Kumazawa T;Ueda T;Nishida T;Soeda T;Okayama S;Watanabe M;Kawata H;Kawakami R;Horii M;Okura H;Uemura S;Hatakeyama K;Sakaguchi Y;Saito Y
越来越多的证据表明，肾上腺素能受体(β-adrenoceptor，AR)的改变，如其偶联G蛋白的脱敏和亚型转换，在心力衰竭时对儿茶酚胺的毒性具有保护作用。然而，在与急性期循环中儿茶酚胺激增相关的人类Takotsubo综合征中，没有组织学证据表明β-AR改变。本研究的目的是探讨β-AR信号的改变在TTS发生机制中的作用。本文对26例TTS患者、19例左心功能正常患者和26例扩张型心肌病(DCM)患者的左心室(LV)标本进行了研究。免疫组织化学结果显示，启动β-AR信号转导的G蛋白偶联受体激酶2和β-arrestin2在心肌梗死急性期较扩张型心肌病和正常对照组表达更丰富。GRK2和β-arrestin2膜染色阳性的心肌细胞在急性期心肌细胞中的百分比也显著高于对照组。两名TTS患者恢复期的连续活检显示，GRK2和β-arrestin2的膜表达随着时间的推移而消退。本研究首次提供了β-ARs改变参与TTS发生发展的组织学证据。
Accumulating evidence indicates alteration of the β-adrenoceptor (AR), such as desensitization and subtype switching of its coupling G protein, plays a role in the protection against catecholamine toxicity in heart failure. However, in human takotsubo syndrome (TTS), which is associated with a surge of circulating catecholamine in the acute phase, there is no histologic evidence of β-AR alteration. The purpose of this study was to investigate the involvement of alteration of β-AR signaling in the mechanism of TTS development. Left ventricular (LV) biopsied samples from 26 patients with TTS, 19 with normal LV function, and 26 with dilated cardiomyopathy (DCM) were studied. G protein-coupled receptor kinase 2 (GRK2) and β-arrestin2, which initiate the alteration of β-AR signaling, were more abundantly expressed in the myocardium in acute-phase TTS than in those of DCM and normal control as indicated by immunohistochemistry. The percentage of cardiomyocytes that showed positive membrane staining for GRK2 and β-arrestin2 was also significantly higher in acute-phase TTS. Sequential biopsies in the recovery-phase for two patients with TTS revealed that membrane expression of GRK2 and β-arrestin2 faded over time. This study provided the first histologic evidence of the involvement of alteration of β-ARs in the development of TTS.
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影响因子：
39.3
作者：
Ghadri JR;Sarcon A;Diekmann J;Bataiosu DR;Cammann VL;Jurisic S;Napp LC;Jaguszewski M;Scherff F;Brugger P;Jäncke L;Seifert B;Bax JJ;Ruschitzka F;Lüscher TF;Templin C;InterTAK Co-investigators:
通讯作者：
InterTAK Co-investigators:
DOI：
10.2741/3898
发表时间：
2011-06-01
期刊：
Frontiers in bioscience (Landmark edition)
影响因子：
--
作者：
Huang ZM;Gold JI;Koch WJ
通讯作者：
Koch WJ
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
影响因子：
3.5
作者：
Cao, Xiancun;Zhou, Chunle;Sun, Hong
通讯作者：
Sun, Hong
影响因子：
24
作者：
Borchert, Thomas;Huebscher, Daniela;Streckfuss-Boemeke, Katrin
通讯作者：
Streckfuss-Boemeke, Katrin
影响因子：
5
作者：
Nef, Holger M.;Moellmann, Helge;Elsaesser, Albrecht
通讯作者：
Elsaesser, Albrecht