RESUMEN
BACKGROUND: Gap junction remodeling is an important cause of ventricular arrhythmia in heart failure. However, it remains unclear whether renal denervation (RDN) regulates gap junction remodeling in heart failure. To explore the effect of RDN on gap junction remodeling in dogs with high-pacing-induced heart failure. METHODS: Fifteen dogs were randomly divided into control (n = 5), heart failure (HF) (n = 5), and RDN+HF (n = 5) group. A high-pacing-induced-heart failure model was established using rapid right ventricular pacing for 4 weeks. The RDN+HF group underwent surgical and chemical ablation of both renal arteries before 4 weeks rapid right ventricular pacing. After 4 weeks, echocardiography, High-Performance Liquid Chromatography-Mass Spectrometry test for norepinephrine and epinephrine, and pathological analysis were performed in the above 3 groups. Further, immunohistochemical staining was used to detect tyrosine hydroxylase, ChaT, connexin 43 (Cx43), and connexin 40 (Cx40). Connexin 43 and Cx40 expression was detected by western blotting. Transmission electron microscopy was used to observe the gap junction. RESULTS: Compared to the control group, myocardial fibrosis and sympathetic hyperactivity were observed in the HF group. Immunohistochemical staining and western blotting showed that Cx40 expression and Cx43 expression was significantly reduced in the HF group. Compared with the HF group, the RDN+HF group showed reduced sympathetic hyperactivity, Cx40 expression, Cx40/Cx43 ratio, and increased Cx43 expression. CONCLUSION: Renal denervation alleviates gap junction remodeling in high-pacing-induced heart failure dogs.
RESUMEN
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.