Alteration of ß-Adrenoceptor Signaling in Left Ventricle of Acute Phase Takotsubo Syndrome: a Human Study.
Sci Rep
; 8(1): 12731, 2018 08 24.
Article
in En
| MEDLINE
| ID: mdl-30143703
ABSTRACT
Accumulating evidence indicates alteration of the ß-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 ß-AR alteration. The purpose of this study was to investigate the involvement of alteration of ß-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 ß-arrestin2, which initiate the alteration of ß-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 ß-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 ß-arrestin2 faded over time. This study provided the first histologic evidence of the involvement of alteration of ß-ARs in the development of TTS.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Signal Transduction
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Receptors, Adrenergic, beta
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Takotsubo Cardiomyopathy
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Heart Ventricles
Limits:
Aged
/
Female
/
Humans
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Male
/
Middle aged
Language:
En
Journal:
Sci Rep
Year:
2018
Document type:
Article
Affiliation country: