Calcium Regulation on the Atrial Regional Difference of Collagen Production Activity in Atrial Fibrogenesis
Background: Atrial fibrosis plays an important role in the genesis of heart failure and atrial fibrillation. The left atrium (LA) exhibits a higher level of fibrosis than the right atrium (RA) in heart failure and atrial arrhythmia. However, the mechanism for the high fibrogenic potential of the LA...
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| Language: | English |
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MDPI AG
2021-06-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/9/6/686 |
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| author | Cheng-Chih Chung Yung-Kuo Lin Yao-Chang Chen Yu-Hsun Kao Yung-Hsin Yeh Yi-Jen Chen |
| author_facet | Cheng-Chih Chung Yung-Kuo Lin Yao-Chang Chen Yu-Hsun Kao Yung-Hsin Yeh Yi-Jen Chen |
| author_sort | Cheng-Chih Chung |
| collection | DOAJ |
| description | Background: Atrial fibrosis plays an important role in the genesis of heart failure and atrial fibrillation. The left atrium (LA) exhibits a higher level of fibrosis than the right atrium (RA) in heart failure and atrial arrhythmia. However, the mechanism for the high fibrogenic potential of the LA fibroblasts remains unclear. Calcium (Ca<sup>2+</sup>) signaling contributes to the pro-fibrotic activities of fibroblasts. This study investigated whether differences in Ca<sup>2+</sup> homeostasis contribute to differential fibrogenesis in LA and RA fibroblasts. Methods: Ca<sup>2+</sup> imaging, a patch clamp assay and Western blotting were performed in isolated rat LA and RA fibroblasts. Results: The LA fibroblasts exhibited a higher Ca<sup>2+</sup> entry and gadolinium-sensitive current compared with the RA fibroblasts. The LA fibroblasts exhibited greater pro-collagen type I, type III, phosphorylated Ca<sup>2+</sup>/calmodulin-dependent protein kinase II (CaMKII), phosphorylated phospholipase C (PLC), stromal interaction molecule 1 (STIM1) and transient receptor potential canonical (TRPC) 3 protein expression compared with RA fibroblasts. In the presence of 1 mmol/L ethylene glycol tetra-acetic acid (EGTA, Ca<sup>2+</sup> chelator), the LA fibroblasts had similar pro-collagen type I, type III and phosphorylated CaMKII expression compared with RA fibroblasts. Moreover, in the presence of KN93 (a CaMKII inhibitor, 10 μmol/L), the LA fibroblasts had similar pro-collagen type I and type III compared with RA fibroblasts. Conclusion: The discrepancy of phosphorylated PLC signaling and gadolinium-sensitive Ca<sup>2+</sup> channels in LA and RA fibroblasts induces different levels of Ca<sup>2+</sup> influx, phosphorylated CaMKII expression and collagen production. |
| first_indexed | 2024-03-10T10:18:52Z |
| format | Article |
| id | doaj.art-cf0420cc56934d2d9664b59bb59c2498 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T10:18:52Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-cf0420cc56934d2d9664b59bb59c24982023-11-22T00:34:59ZengMDPI AGBiomedicines2227-90592021-06-019668610.3390/biomedicines9060686Calcium Regulation on the Atrial Regional Difference of Collagen Production Activity in Atrial FibrogenesisCheng-Chih Chung0Yung-Kuo Lin1Yao-Chang Chen2Yu-Hsun Kao3Yung-Hsin Yeh4Yi-Jen Chen5Division of Cardiology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, TaiwanDivision of Cardiology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, TaiwanDepartment of Biomedical Engineering, National Defense Medical Center, Taipei 11490, TaiwanGraduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 11031, TaiwanDivision of Cardiology, Chang Gung Memorial Hospital, Taoyuan 33305, TaiwanDivision of Cardiology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, TaiwanBackground: Atrial fibrosis plays an important role in the genesis of heart failure and atrial fibrillation. The left atrium (LA) exhibits a higher level of fibrosis than the right atrium (RA) in heart failure and atrial arrhythmia. However, the mechanism for the high fibrogenic potential of the LA fibroblasts remains unclear. Calcium (Ca<sup>2+</sup>) signaling contributes to the pro-fibrotic activities of fibroblasts. This study investigated whether differences in Ca<sup>2+</sup> homeostasis contribute to differential fibrogenesis in LA and RA fibroblasts. Methods: Ca<sup>2+</sup> imaging, a patch clamp assay and Western blotting were performed in isolated rat LA and RA fibroblasts. Results: The LA fibroblasts exhibited a higher Ca<sup>2+</sup> entry and gadolinium-sensitive current compared with the RA fibroblasts. The LA fibroblasts exhibited greater pro-collagen type I, type III, phosphorylated Ca<sup>2+</sup>/calmodulin-dependent protein kinase II (CaMKII), phosphorylated phospholipase C (PLC), stromal interaction molecule 1 (STIM1) and transient receptor potential canonical (TRPC) 3 protein expression compared with RA fibroblasts. In the presence of 1 mmol/L ethylene glycol tetra-acetic acid (EGTA, Ca<sup>2+</sup> chelator), the LA fibroblasts had similar pro-collagen type I, type III and phosphorylated CaMKII expression compared with RA fibroblasts. Moreover, in the presence of KN93 (a CaMKII inhibitor, 10 μmol/L), the LA fibroblasts had similar pro-collagen type I and type III compared with RA fibroblasts. Conclusion: The discrepancy of phosphorylated PLC signaling and gadolinium-sensitive Ca<sup>2+</sup> channels in LA and RA fibroblasts induces different levels of Ca<sup>2+</sup> influx, phosphorylated CaMKII expression and collagen production.https://www.mdpi.com/2227-9059/9/6/686fibroblastsheart failureleft atriumright atriumCa<sup>2+</sup>CaMKII |
| spellingShingle | Cheng-Chih Chung Yung-Kuo Lin Yao-Chang Chen Yu-Hsun Kao Yung-Hsin Yeh Yi-Jen Chen Calcium Regulation on the Atrial Regional Difference of Collagen Production Activity in Atrial Fibrogenesis Biomedicines fibroblasts heart failure left atrium right atrium Ca<sup>2+</sup> CaMKII |
| title | Calcium Regulation on the Atrial Regional Difference of Collagen Production Activity in Atrial Fibrogenesis |
| title_full | Calcium Regulation on the Atrial Regional Difference of Collagen Production Activity in Atrial Fibrogenesis |
| title_fullStr | Calcium Regulation on the Atrial Regional Difference of Collagen Production Activity in Atrial Fibrogenesis |
| title_full_unstemmed | Calcium Regulation on the Atrial Regional Difference of Collagen Production Activity in Atrial Fibrogenesis |
| title_short | Calcium Regulation on the Atrial Regional Difference of Collagen Production Activity in Atrial Fibrogenesis |
| title_sort | calcium regulation on the atrial regional difference of collagen production activity in atrial fibrogenesis |
| topic | fibroblasts heart failure left atrium right atrium Ca<sup>2+</sup> CaMKII |
| url | https://www.mdpi.com/2227-9059/9/6/686 |
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