Alteration of β-Adrenoceptor Signaling in Left Ventricle of Acute Phase Takotsubo Syndrome: a Human Study

• Published in: Scientific reports Vol. 8; no. 1; pp. 12731 - 11
• Main Authors: Nakano, Tomoya, Onoue, Kenji, Nakada, Yasuki, Nakagawa, Hitoshi, Kumazawa, Takuya, Ueda, Tomoya, Nishida, Taku, Soeda, Tsunenari, Okayama, Satoshi, Watanabe, Makoto, Kawata, Hiroyuki, Kawakami, Rika, Horii, Manabu, Okura, Hiroyuki, Uemura, Shiro, Hatakeyama, Kinta, Sakaguchi, Yasuhiro, Saito, Yoshihiko
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 24.08.2018; Nature Publishing Group
• Subjects: 13/1; 13/51; 692/4019/592/75/230; 692/4019/592/75/74/1540; Adrenergic receptors; b-Adrenergic-receptor kinase; Cardiomyocytes; Cardiomyopathy; Catecholamines; Dilated cardiomyopathy; G protein-coupled receptor kinase; G protein-coupled receptor kinase 2; Heart diseases; Humanities and Social Sciences; Immunohistochemistry; Kinases; multidisciplinary; Myocardium; Science; Science (multidisciplinary); Toxicity; Ventricle
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-018-31034-z

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.