Desmosomal Junctions and Connexin-43 Remodeling in High-Pacing-Induced Heart Failure Dogs
Qing Wang1, Liang Xiaoyan1, Shuai Shang1
1Department of Pacing and Electrophysiology, The First Affiliated Hospital of Xinjiang Medical University, Xinjiang, China; Xinjiang Key Laboratory of Cardiac Electrophysiology and Cardiac Remodeling, The First Affiliated Hospital of Xinjiang Medical University, Xinjiang, China.
Background:
While desmosomal junctions and gap junction remodeling are among the arrhythmogenic substrates, the fate of desmosomal and gap junctions in high-pacing-induced heart failure remains unclear. This aim of this study was to determine the fate of desmosomal junctions in high-pacing-induced heart failure.
Methods:
Dogs were randomly divided into 2 equal groups, a high-pacing-induced heart failure model group (heart failure group, n = 6) and a sham operation group (control group, n = 6). Echocardiography and cardiac electrophysiological examination were performed. Cardiac tissue was analyzed by immunofluorescence and transmission electron microscopy. The expression of desmoplakin and desmoglein-2 proteins was detected by western blot.
Results:
A significant decrease in ejection fraction, significant cardiac dilatation, diastolic and systolic dysfunction, and ventricular thinning occurred after 4 weeks in high-pacing-induced dog model of heart failure. Effective refractory period action potential duration at 90% repolarization was prolonged in the heart failure group. Immunofluorescence analysis and transmission electron microscopy demonstrated connexin-43 lateralization accompanies desmoglein-2 and desmoplakin remodeling in the heart failure group. Western blotting showed that the expression of desmoplakin and desmoglein-2 proteins was higher in heart failure than in normal tissue.
Conclusion:
Desmosome (desmoglein-2 and desmoplakin) redistribution and desmosome (desmoglein-2) overexpression accompanying connexin-43 lateralization were parts of a complex remodeling in high-pacing-induced heart failure.
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