J Vila1, R Pariaut2, N S Moïse3, E M Oxford3, P R Fox4, C A Reynolds1, C Saelinger1. 1. Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, 70806, USA. 2. Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, 70806, USA; Department of Clinical Sciences, Cornell University College of Veterinary Medicine, Ithaca, NY, 14850, USA. Electronic address: rp223@cornell.edu. 3. Department of Clinical Sciences, Cornell University College of Veterinary Medicine, Ithaca, NY, 14850, USA. 4. Caspary Institute, The Animal Medical Center, New York, NY, 10065, USA.
Abstract
OBJECTIVE: To investigate the expression and distribution of desmosomal and gap junction proteins of the intercalated disc in the atria of boxers with arrhythmogenic right ventricular cardiomyopathy (ARVC). ANIMALS: Nineteen control dogs and 13 boxers with histopathologically confirmed ARVC. METHODS: Right and left atrial samples were examined using immunofluorescence and Western blots. The intercalated disc proteins investigated included total and phosphorylated connexin43 (Cx43 and pCx43), connexin45, connexin40, plakoglobin, plakophilin-2, desmoplakin, and N-cadherin. RESULTS: Histopathological changes characteristic of ARVC were present in the left or right atrium of 12 out of 13 boxers and were absent in all control dogs. When compared to the 19 control dogs, immunofluorescence analysis revealed a decrease in signal intensity for pCx43 and plakoglobin in the left (p = 0.03 and p = 0.014, respectively) and right atrium (p = 0.015 and p = 0.002, respectively) of affected boxers. Connexin43 and pCx43 Western blot band density was significantly decreased in the left (p = 0.025 and p = 0.027, respectively) and right atrium (p = 0.001 and p = 0.044, respectively) of affected boxers. CONCLUSION: Altered intercalated disc and gap junction proteins were identified in atrial myocardium of ARVC boxers, supporting atrial involvement as part of this disorder. Reduction in pCx43 in conjunction with histological changes could represent the substrate for atrial arrhythmias associated with ARVC. Furthermore, these findings detected in boxer dogs, lend support for the broader term, arrhythmogenic cardiomyopathy, as preferred nomenclature used to describe this disease in humans.
OBJECTIVE: To investigate the expression and distribution of desmosomal and gap junction proteins of the intercalated disc in the atria of boxers with arrhythmogenic right ventricular cardiomyopathy (ARVC). ANIMALS: Nineteen control dogs and 13 boxers with histopathologically confirmed ARVC. METHODS: Right and left atrial samples were examined using immunofluorescence and Western blots. The intercalated disc proteins investigated included total and phosphorylated connexin43 (Cx43 and pCx43), connexin45, connexin40, plakoglobin, plakophilin-2, desmoplakin, and N-cadherin. RESULTS: Histopathological changes characteristic of ARVC were present in the left or right atrium of 12 out of 13 boxers and were absent in all control dogs. When compared to the 19 control dogs, immunofluorescence analysis revealed a decrease in signal intensity for pCx43 and plakoglobin in the left (p = 0.03 and p = 0.014, respectively) and right atrium (p = 0.015 and p = 0.002, respectively) of affected boxers. Connexin43 and pCx43 Western blot band density was significantly decreased in the left (p = 0.025 and p = 0.027, respectively) and right atrium (p = 0.001 and p = 0.044, respectively) of affected boxers. CONCLUSION: Altered intercalated disc and gap junction proteins were identified in atrial myocardium of ARVC boxers, supporting atrial involvement as part of this disorder. Reduction in pCx43 in conjunction with histological changes could represent the substrate for atrial arrhythmias associated with ARVC. Furthermore, these findings detected in boxer dogs, lend support for the broader term, arrhythmogenic cardiomyopathy, as preferred nomenclature used to describe this disease in humans.
Authors: Guoliang Li; Guy H Fontaine; Shuanliang Fan; Yang Yan; Peter K Bode; Firat Duru; Robert Frank; Ardan M Saguner Journal: Cardiol J Date: 2018-11-05 Impact factor: 2.737
Authors: Iris Ribitsch; Pedro M Baptista; Anna Lange-Consiglio; Luca Melotti; Marco Patruno; Florien Jenner; Eva Schnabl-Feichter; Luke C Dutton; David J Connolly; Frank G van Steenbeek; Jayesh Dudhia; Louis C Penning Journal: Front Bioeng Biotechnol Date: 2020-08-13