Language
English
Publication Date
6-23-2023
Journal
Circulation Research
DOI
10.1161/CIRCRESAHA.122.322213
PMID
37154033
PMCID
PMC10330339
PubMedCentral® Posted Date
6-23-2024
PubMedCentral® Full Text Version
Author MSS
Abstract
BACKGROUND: Atrial fibrillation (AF), the most common arrhythmia, is associated with the downregulation of
METHODS: Right atrial samples from patients with AF were used to assess the protein levels of FKBP5. A cardiomyocyte-specific FKBP5 knockdown mouse model was established by crossbreeding
RESULTS: FKBP5 protein levels were lower in the atrial lysates of patients with paroxysmal AF or long-lasting persistent (chronic) AF. Cardiomyocyte-specific knockdown mice exhibited increased AF inducibility and duration compared with control mice. Enhanced AF susceptibility in cardiomyocyte-specific knockdown mice was associated with the development of action potential alternans and spontaneous Ca
CONCLUSIONS: This is the first study to demonstrate a role for the FKBP5-deficiency in atrial arrhythmogenesis and to establish FKBP5 as a negative regulator of hypoxia-inducible factor 1α in cardiomyocytes. Our results identify a potential molecular mechanism for the proarrhythmic NCX1 upregulation in chronic AF patients.
Keywords
Mice, Animals, Atrial Fibrillation, Down-Regulation, Myocytes, Cardiac, Hypoxia, Heat-Shock Proteins
Published Open-Access
yes
Recommended Citation
Wang, Xiaolei; Song, Jia; Yuan, Yue; et al., "Downregulation of FKBP5 Promotes Atrial Arrhythmogenesis" (2023). Faculty and Staff Publications. 676.
https://digitalcommons.library.tmc.edu/baylor_docs/676
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