Abstract
Intermittent hypoxia (IH) has been extensively studied in recent years, demonstrating adverse and beneficial effects on several physiological systems. However, the precise mechanism underlying its cardiac effects on the heart remains unclear. This study aims to explore the effect of treatment on atrial fibrillation under IH conditions, providing data that can potentially be used in the treatment of heart disease. An atrial fibrillation (AF) model was induced by injecting monocrotaline (MCT, 60 mg/kg) into rats. The study included 32 rats divided into four groups: Control, Control + IH, AF, and AF + IH. We evaluated molecular changes associated with AF using ELISA and Western blot and performed electrophysiological experiments to evaluate AF. Arrhythmia-related calcium and fibrosis markers were investigated. Phosphorylation levels of CaMKII, Phospholamban, and RyR2 all increased in the AF group but decreased in the IH-exposed group. Additionally, fibrosis marker expressions such as SMA, MMP2, MMP9, and TGF-β increased in the AF group but were significantly downregulated with IH treatment. Connexin 43 and AQP4 expression were restored in the IH-treated group. These findings suggest that IH may prevent AF by downregulating the expression of calcium-handling proteins and fibrosis-associated proteins in an AF-induced rat model.
Keywords:
Aquaporin 4; arrhythmia; atrial fibrillation; cardiac remodeling; intermittent hypoxia.
MeSH terms
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Animals
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Aquaporin 4
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Atrial Fibrillation* / etiology
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Atrial Fibrillation* / metabolism
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Calcium / metabolism
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Calcium-Binding Proteins / metabolism
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Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism
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Connexin 43 / metabolism
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Disease Models, Animal
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Fibrosis
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Hypoxia* / metabolism
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Male
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Matrix Metalloproteinase 2 / metabolism
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Phosphorylation
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Rats
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Rats, Sprague-Dawley
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Ryanodine Receptor Calcium Release Channel / metabolism
Substances
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Ryanodine Receptor Calcium Release Channel
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phospholamban
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Calcium-Binding Proteins
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Connexin 43
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Calcium-Calmodulin-Dependent Protein Kinase Type 2
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RyR2 protein, rat
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Calcium
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Aqp4 protein, rat
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Matrix Metalloproteinase 2
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Aquaporin 4
Grants and funding
The present study was supported by research grants from the Basic Science Research Program through the National Research Foundation of Korea (NRF-2018R1A6A1A03025523, 2019R1C1C1003389, 2022R1A2C1093352, RS-2024-00336974) and the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health and Welfare, Republic of Korea (grant number: RS-2023-00266209). This work was also supported by the Institute of Information and Communications Technology Planning and Evaluation (IITP) grant funded by the Korean government (MSIT) (No. RS-2022-00155966, Artificial Intelligence Convergence Innovation Human Resources Development (Ewha Womans University)). Hyewon Park was supported by an RP-Grant 2021 of Ewha Womans University.