Maintenance and Reversibility of Paroxysmal Atrial Fibrillation in JDP2 Overexpressing Mice
Heart-specific overexpression of transcriptional regulator JDP2 (jun dimerization protein 2) for 5 weeks provokes paroxysmal atrial fibrillation (AF) in mice. We now investigated whether AF and atrial remodeling will be reversible upon termination of JDP2 overexpression, and whether paroxysmal AF co...
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2025-07-01
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| author | Gerhild Euler Jacqueline Heger Marcel Rossol Rainer Schulz Mariana Parahuleva Jens Kockskämper |
| author_facet | Gerhild Euler Jacqueline Heger Marcel Rossol Rainer Schulz Mariana Parahuleva Jens Kockskämper |
| author_sort | Gerhild Euler |
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| description | Heart-specific overexpression of transcriptional regulator JDP2 (jun dimerization protein 2) for 5 weeks provokes paroxysmal atrial fibrillation (AF) in mice. We now investigated whether AF and atrial remodeling will be reversible upon termination of JDP2 overexpression, and whether paroxysmal AF converts to permanent AF in the presence of maintained JDP2 overexpression. Cardiac-specific JDP2 overexpression for 5 weeks, resulting in paroxysmal AF, was either continued or repressed via a tet-off system for another 5 weeks. ECGs were recorded weekly. Thereafter, heart and lung weights, and atrial mRNA and protein expression were determined. Extending JDP2 overexpression did not aggravate the AF phenotype, still paroxysmal AF, prolongation of PQ intervals, and atrial hypertrophy were present. This phenotype was completely reversible upon cessation of JDP2 overexpression. A massive downregulation of connexin40 and calcium handling proteins, including SERCA2a, calsequestrin, and ryanodine receptor, was observed in atria after prolonged JDP2 overexpression. In conclusion, atrial remodeling and paroxysmal AF under JDP2 overexpression are not sufficient to maintain or aggravate AF in the absence of JDP2. The comparison of the two groups indicates that the downregulation of calcium proteins and connexins is an important factor in the maintenance of the disease. |
| format | Article |
| id | doaj-art-83a8c7878a90409fb9734dfbfbc0a9b8 |
| institution | DOAJ |
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| language | English |
| publishDate | 2025-07-01 |
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| spelling | doaj-art-83a8c7878a90409fb9734dfbfbc0a9b82025-08-20T03:08:00ZengMDPI AGCells2073-44092025-07-011414107910.3390/cells14141079Maintenance and Reversibility of Paroxysmal Atrial Fibrillation in JDP2 Overexpressing MiceGerhild Euler0Jacqueline Heger1Marcel Rossol2Rainer Schulz3Mariana Parahuleva4Jens Kockskämper5Institute of Physiology, Justus Liebig University, 35392 Giessen, GermanyInstitute of Physiology, Justus Liebig University, 35392 Giessen, GermanyBiochemical-Pharmacological Centre (BPC) Marburg, Institute of Pharmacology and Clinical Pharmacy, University of Marburg, 35043 Marburg, GermanyInstitute of Physiology, Justus Liebig University, 35392 Giessen, GermanyInternal Medicine/Cardiology and Angiology, University Hospital of Giessen and Marburg, 35033 Marburg, GermanyBiochemical-Pharmacological Centre (BPC) Marburg, Institute of Pharmacology and Clinical Pharmacy, University of Marburg, 35043 Marburg, GermanyHeart-specific overexpression of transcriptional regulator JDP2 (jun dimerization protein 2) for 5 weeks provokes paroxysmal atrial fibrillation (AF) in mice. We now investigated whether AF and atrial remodeling will be reversible upon termination of JDP2 overexpression, and whether paroxysmal AF converts to permanent AF in the presence of maintained JDP2 overexpression. Cardiac-specific JDP2 overexpression for 5 weeks, resulting in paroxysmal AF, was either continued or repressed via a tet-off system for another 5 weeks. ECGs were recorded weekly. Thereafter, heart and lung weights, and atrial mRNA and protein expression were determined. Extending JDP2 overexpression did not aggravate the AF phenotype, still paroxysmal AF, prolongation of PQ intervals, and atrial hypertrophy were present. This phenotype was completely reversible upon cessation of JDP2 overexpression. A massive downregulation of connexin40 and calcium handling proteins, including SERCA2a, calsequestrin, and ryanodine receptor, was observed in atria after prolonged JDP2 overexpression. In conclusion, atrial remodeling and paroxysmal AF under JDP2 overexpression are not sufficient to maintain or aggravate AF in the absence of JDP2. The comparison of the two groups indicates that the downregulation of calcium proteins and connexins is an important factor in the maintenance of the disease.https://www.mdpi.com/2073-4409/14/14/1079atrial hypertrophycalciumconnexinECGJDP2paroxysmal atrial fibrillation |
| spellingShingle | Gerhild Euler Jacqueline Heger Marcel Rossol Rainer Schulz Mariana Parahuleva Jens Kockskämper Maintenance and Reversibility of Paroxysmal Atrial Fibrillation in JDP2 Overexpressing Mice Cells atrial hypertrophy calcium connexin ECG JDP2 paroxysmal atrial fibrillation |
| title | Maintenance and Reversibility of Paroxysmal Atrial Fibrillation in JDP2 Overexpressing Mice |
| title_full | Maintenance and Reversibility of Paroxysmal Atrial Fibrillation in JDP2 Overexpressing Mice |
| title_fullStr | Maintenance and Reversibility of Paroxysmal Atrial Fibrillation in JDP2 Overexpressing Mice |
| title_full_unstemmed | Maintenance and Reversibility of Paroxysmal Atrial Fibrillation in JDP2 Overexpressing Mice |
| title_short | Maintenance and Reversibility of Paroxysmal Atrial Fibrillation in JDP2 Overexpressing Mice |
| title_sort | maintenance and reversibility of paroxysmal atrial fibrillation in jdp2 overexpressing mice |
| topic | atrial hypertrophy calcium connexin ECG JDP2 paroxysmal atrial fibrillation |
| url | https://www.mdpi.com/2073-4409/14/14/1079 |
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