{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T07:41:30Z","timestamp":1788853290150,"version":"build-2803163510"},"reference-count":25,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2020,11,30]],"date-time":"2020-11-30T00:00:00Z","timestamp":1606694400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Background: Cardiac-specific JDP2 overexpression provokes ventricular dysfunction and atrial dilatation in mice. We performed in vivo studies on JDP2-overexpressing mice to investigate the impact of JDP2 on the predisposition to spontaneous atrial fibrillation (AF). Methods: JDP2-overexpression was started by withdrawal of a doxycycline diet in 4-week-old mice. The spontaneous onset of AF was documented by ECG within 4 to 5 weeks of JDP2 overexpression. Gene expression was analyzed by real-time RT-PCR and Western blots. Results: In atrial tissue of JDP2 mice, besides the 3.6-fold increase of JDP2 mRNA, no changes could be detected within one week of JDP2 overexpression. Atrial dilatation and hypertrophy, combined with elongated cardiomyocytes and fibrosis, became evident after 5 weeks of JDP2 overexpression. Electrocardiogram (ECG) recordings revealed prolonged PQ-intervals and broadened P-waves and QRS-complexes, as well as AV-blocks and paroxysmal AF. Furthermore, reductions were found in the atrial mRNA and protein level of the calcium-handling proteins NCX, Cav1.2 and RyR2, as well as of connexin40 mRNA. mRNA of the hypertrophic marker gene ANP, pro-inflammatory MCP1, as well as markers of immune cell infiltration (CD68, CD20) were increased in JDP2 mice. Conclusion: JDP2 is an important regulator of atrial calcium and immune homeostasis and is involved in the development of atrial conduction defects and arrhythmogenic substrates preceding paroxysmal AF.<\/jats:p>","DOI":"10.3390\/ijms21239095","type":"journal-article","created":{"date-parts":[[2020,11,30]],"date-time":"2020-11-30T10:26:12Z","timestamp":1606731972000},"page":"9095","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Structural, Pro-Inflammatory and Calcium Handling Remodeling Underlies Spontaneous Onset of Paroxysmal Atrial Fibrillation in JDP2-Overexpressing Mice"],"prefix":"10.3390","volume":"21","author":[{"given":"Mariana S.","family":"Parahuleva","sequence":"first","affiliation":[{"name":"Internal Medicine\/Cardiology and Angiology, University Hospital of Giessen and Marburg, 35033 Marburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens","family":"Kocksk\u00e4mper","sequence":"additional","affiliation":[{"name":"Biochemical-Pharmacological Centre (BPC) Marburg, Institute of Pharmacology and Clinical Pharmacy, University of Marburg, 35043 Marburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline","family":"Heger","sequence":"additional","affiliation":[{"name":"Institute of Physiology, Justus Liebig University, 35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3843-6216","authenticated-orcid":false,"given":"Wolfram","family":"Grimm","sequence":"additional","affiliation":[{"name":"Internal Medicine\/Cardiology and Angiology, University Hospital of Giessen and Marburg, 35033 Marburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Scherer","sequence":"additional","affiliation":[{"name":"Biochemical-Pharmacological Centre (BPC) Marburg, Institute of Pharmacology and Clinical Pharmacy, University of Marburg, 35043 Marburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"B\u00fchler","sequence":"additional","affiliation":[{"name":"Biochemical-Pharmacological Centre (BPC) Marburg, Institute of Pharmacology and Clinical Pharmacy, University of Marburg, 35043 Marburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9498-9558","authenticated-orcid":false,"given":"Julian","family":"Kreutz","sequence":"additional","affiliation":[{"name":"Internal Medicine\/Cardiology and Angiology, University Hospital of Giessen and Marburg, 35033 Marburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3017-0476","authenticated-orcid":false,"given":"Rainer","family":"Schulz","sequence":"additional","affiliation":[{"name":"Institute of Physiology, Justus Liebig University, 35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9094-773X","authenticated-orcid":false,"given":"Gerhild","family":"Euler","sequence":"additional","affiliation":[{"name":"Institute of Physiology, Justus Liebig University, 35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,11,30]]},"reference":[{"key":"ref_1","unstructured":"Hindricks, G., Potpara, T., Dagres, N., Arbelo, E., Bax, J.J., Blomstr\u00f6m-Lundqvist, C., Boriani, G., Castella, M., Dan, G.A., and Dilaveris, P.E. 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