並列タイトル等急性期たこつぼ症候群症例の心内膜心筋生検を用いた左室心筋細胞におけるβ-アドレナリン受容体シグナル動態の検討
一般注記type:Thesis
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.
博士（医学）・甲第701号・平成31年3月15日
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© 2018 Springer Nature Publishing AG
identifier:Scientific reports Vol.8 No.1 Article No.12731 (2018 Aug)
identifier:20452322
identifier:http://ginmu.naramed-u.ac.jp/dspace/handle/10564/3549
identifier:Scientific reports, 8(1): Article No.12731
DOIinfo:doi/10.1038/s41598-018-31034-z
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