Maintenance and Reversibility of Paroxysmal Atrial Fibrillation in JDP2 Overexpressing Mice
Gerhild Euler, Jacqueline Heger, Marcel Rossol, Rainer Schulz, Mariana Parahuleva, Jens Kockskämper
TL;DR
Overexpression of JDP2 in mice hearts causes paroxysmal atrial fibrillation, which is reversible when JDP2 levels are reduced.
Contribution
The study shows that JDP2 overexpression causes reversible paroxysmal AF and identifies downregulation of calcium and connexin proteins as key factors.
Findings
Paroxysmal AF and atrial remodeling are reversible after stopping JDP2 overexpression.
Prolonged JDP2 overexpression leads to downregulation of connexin40 and calcium handling proteins.
Continued JDP2 overexpression does not convert paroxysmal AF to permanent AF.
Abstract
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…
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Taxonomy
TopicsCardiac electrophysiology and arrhythmias · Atrial Fibrillation Management and Outcomes · Cardiac Arrhythmias and Treatments