Increased expression of six-large extracellular vesicle-derived miRNAs signature for nonvalvular atrial fibrillation
Abstract Backgrounds Non-valvular atrial fibrillation (AF) is the most common type of cardiac arrhythmia. AF is caused by electrophysiological abnormalities and alteration of atrial tissues, which leads to the generation of abnormal electrical impulses. Extracellular vesicles (EVs) are membrane-boun...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-01-01
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| Series: | Journal of Translational Medicine |
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| Online Access: | https://doi.org/10.1186/s12967-021-03213-6 |
| _version_ | 1798033441589035008 |
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| author | Panjaree Siwaponanan Pontawee Kaewkumdee Wilasinee Phromawan Suthipol Udompunturak Nusara Chomanee Kamol Udol Kovit Pattanapanyasat Rungroj Krittayaphong |
| author_facet | Panjaree Siwaponanan Pontawee Kaewkumdee Wilasinee Phromawan Suthipol Udompunturak Nusara Chomanee Kamol Udol Kovit Pattanapanyasat Rungroj Krittayaphong |
| author_sort | Panjaree Siwaponanan |
| collection | DOAJ |
| description | Abstract Backgrounds Non-valvular atrial fibrillation (AF) is the most common type of cardiac arrhythmia. AF is caused by electrophysiological abnormalities and alteration of atrial tissues, which leads to the generation of abnormal electrical impulses. Extracellular vesicles (EVs) are membrane-bound vesicles released by all cell types. Large EVs (lEVs) are secreted by the outward budding of the plasma membrane during cell activation or cell stress. lEVs are thought to act as vehicles for miRNAs to modulate cardiovascular function, and to be involved in the pathophysiology of cardiovascular diseases (CVDs), including AF. This study identified lEV-miRNAs that were differentially expressed between AF patients and non-AF controls. Methods lEVs were isolated by differential centrifugation and characterized by Nanoparticle Tracking Analysis (NTA), Transmission Electron Microscopy (TEM), flow cytometry and Western blot analysis. For the discovery phase, 12 AF patients and 12 non-AF controls were enrolled to determine lEV-miRNA profile using quantitative reverse transcription polymerase chain reaction array. The candidate miRNAs were confirmed their expression in a validation cohort using droplet digital PCR (30 AF, 30 controls). Bioinformatics analysis was used to predict their target genes and functional pathways. Results TEM, NTA and flow cytometry demonstrated that lEVs presented as cup shape vesicles with a size ranging from 100 to 1000 nm. AF patients had significantly higher levels of lEVs at the size of 101–200 nm than non-AF controls. Western blot analysis was used to confirm EV markers and showed the high level of cardiomyocyte expression (Caveolin-3) in lEVs from AF patients. Nineteen miRNAs were significantly higher (> twofold, p < 0.05) in AF patients compared to non-AF controls. Six highly expressed miRNAs (miR-106b-3p, miR-590-5p, miR-339-3p, miR-378-3p, miR-328-3p, and miR-532-3p) were selected to confirm their expression. Logistic regression analysis showed that increases in the levels of these 6 highly expressed miRNAs associated with AF. The possible functional roles of these lEV-miRNAs may involve in arrhythmogenesis, cell apoptosis, cell proliferation, oxygen hemostasis, and structural remodeling in AF. Conclusion Increased expression of six lEV-miRNAs reflects the pathophysiology of AF that may provide fundamental knowledge to develop the novel biomarkers for diagnosis or monitoring the patients with the high risk of AF. |
| first_indexed | 2024-04-11T20:30:30Z |
| format | Article |
| id | doaj.art-895cbfabf95d41fd952c4a6e73429453 |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-04-11T20:30:30Z |
| publishDate | 2022-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-895cbfabf95d41fd952c4a6e734294532022-12-22T04:04:31ZengBMCJournal of Translational Medicine1479-58762022-01-0120111610.1186/s12967-021-03213-6Increased expression of six-large extracellular vesicle-derived miRNAs signature for nonvalvular atrial fibrillationPanjaree Siwaponanan0Pontawee Kaewkumdee1Wilasinee Phromawan2Suthipol Udompunturak3Nusara Chomanee4Kamol Udol5Kovit Pattanapanyasat6Rungroj Krittayaphong7Siriraj Center of Research Excellence for Microparticle and Exosome in Diseases, Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol UniversityDivision of Cardiology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol UniversityDivision of Cardiology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol UniversityDivision of Clinical Epidemiology, Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol UniversityDepartment of Pathology, Faculty of Medicine Siriraj Hospital, Mahidol UniversityDepartment of Preventive and Social Medicine, Faculty of Medicine Siriraj Hospital, Mahidol UniversitySiriraj Center of Research Excellence for Microparticle and Exosome in Diseases, Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol UniversityDivision of Cardiology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol UniversityAbstract Backgrounds Non-valvular atrial fibrillation (AF) is the most common type of cardiac arrhythmia. AF is caused by electrophysiological abnormalities and alteration of atrial tissues, which leads to the generation of abnormal electrical impulses. Extracellular vesicles (EVs) are membrane-bound vesicles released by all cell types. Large EVs (lEVs) are secreted by the outward budding of the plasma membrane during cell activation or cell stress. lEVs are thought to act as vehicles for miRNAs to modulate cardiovascular function, and to be involved in the pathophysiology of cardiovascular diseases (CVDs), including AF. This study identified lEV-miRNAs that were differentially expressed between AF patients and non-AF controls. Methods lEVs were isolated by differential centrifugation and characterized by Nanoparticle Tracking Analysis (NTA), Transmission Electron Microscopy (TEM), flow cytometry and Western blot analysis. For the discovery phase, 12 AF patients and 12 non-AF controls were enrolled to determine lEV-miRNA profile using quantitative reverse transcription polymerase chain reaction array. The candidate miRNAs were confirmed their expression in a validation cohort using droplet digital PCR (30 AF, 30 controls). Bioinformatics analysis was used to predict their target genes and functional pathways. Results TEM, NTA and flow cytometry demonstrated that lEVs presented as cup shape vesicles with a size ranging from 100 to 1000 nm. AF patients had significantly higher levels of lEVs at the size of 101–200 nm than non-AF controls. Western blot analysis was used to confirm EV markers and showed the high level of cardiomyocyte expression (Caveolin-3) in lEVs from AF patients. Nineteen miRNAs were significantly higher (> twofold, p < 0.05) in AF patients compared to non-AF controls. Six highly expressed miRNAs (miR-106b-3p, miR-590-5p, miR-339-3p, miR-378-3p, miR-328-3p, and miR-532-3p) were selected to confirm their expression. Logistic regression analysis showed that increases in the levels of these 6 highly expressed miRNAs associated with AF. The possible functional roles of these lEV-miRNAs may involve in arrhythmogenesis, cell apoptosis, cell proliferation, oxygen hemostasis, and structural remodeling in AF. Conclusion Increased expression of six lEV-miRNAs reflects the pathophysiology of AF that may provide fundamental knowledge to develop the novel biomarkers for diagnosis or monitoring the patients with the high risk of AF.https://doi.org/10.1186/s12967-021-03213-6Large extracellular vesiclesmiRNABiomarkersPatientsAtrial fibrillation |
| spellingShingle | Panjaree Siwaponanan Pontawee Kaewkumdee Wilasinee Phromawan Suthipol Udompunturak Nusara Chomanee Kamol Udol Kovit Pattanapanyasat Rungroj Krittayaphong Increased expression of six-large extracellular vesicle-derived miRNAs signature for nonvalvular atrial fibrillation Journal of Translational Medicine Large extracellular vesicles miRNA Biomarkers Patients Atrial fibrillation |
| title | Increased expression of six-large extracellular vesicle-derived miRNAs signature for nonvalvular atrial fibrillation |
| title_full | Increased expression of six-large extracellular vesicle-derived miRNAs signature for nonvalvular atrial fibrillation |
| title_fullStr | Increased expression of six-large extracellular vesicle-derived miRNAs signature for nonvalvular atrial fibrillation |
| title_full_unstemmed | Increased expression of six-large extracellular vesicle-derived miRNAs signature for nonvalvular atrial fibrillation |
| title_short | Increased expression of six-large extracellular vesicle-derived miRNAs signature for nonvalvular atrial fibrillation |
| title_sort | increased expression of six large extracellular vesicle derived mirnas signature for nonvalvular atrial fibrillation |
| topic | Large extracellular vesicles miRNA Biomarkers Patients Atrial fibrillation |
| url | https://doi.org/10.1186/s12967-021-03213-6 |
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