Title page for ETD etd-10162012-191021
|Type of Document
||Vila, Jorge Luis
|Author's Email Address
||Structural and Molecular Pathology of the Atrium in Boxer Arrhythmogenic Cardiomyopathy
||Master of Science (M.S.)
||Veterinary Clinical Sciences
- arrhythmogenic right ventricular cardiomyopathy
|Date of Defense
Arrhythmogenic cardiomyopathy (AC), also known as arrhythmogenic right ventricular cardiomyopathy (ARVC), is a disease characterized by fatty or fibro-fatty myocardial replacement, predominantly in the right ventricle and to a lower extent the left ventricle. It is recognized as a disease affecting the cardiac intercalated disc. Clinically, it is associated with ventricular arrhythmias, although atrial arrhythmias and atrial histopathological changes characteristic of AC have occasionally been reported. The full extent of atrial involvement in AC has not been investigated. Therefore, we aimed to apply histopathology, immunochemical detection, immunolocalization and transmission electron microscopy (TEM) techniques to characterize the distribution of desmosomal and gap junction proteins at the intercalated disc in the atria of boxers with AC. We hypothesized that histological changes consistent with AC and alterations to the intercalated disc proteins are present in the atria of boxer dogs with AC. The hearts from 14 control and 13 boxers with confirmed AC were studied. Right and left atrial sections from 11 boxers were examined by immunofluorescence. Samples from 10 boxers were used for Western blot analysis. The intercalated disc proteins investigated were connexin 43 (Cx43), connexin 45, connexin 40, plakoglobin, plakophilin-2, desmoplakin, and cadherin. Transmission electron microscopy was performed on the right and left atrial sections of 2 boxers and 2 controls. Western blot band relative density indicated a significant decrease of Cx43 in the right atrium of affected boxers compared to controls. There was no difference between controls and boxers for the other proteins investigated. Immunofluorescence analysis showed that the number of Cx43 signals and the signal intensity for plakoglobin was decreased in the left and right atrium of affected boxers. Transmission electron microscopy suggested disruption of the intercalated disc in affected boxers. In conclusion, these results indicate the alteration of intercalated disc proteins in the atrial myocardium of boxers, showing atrial involvement in addition to the ventricles. These findings support the use of the broader term of AC rather than ARVC to describe this disease. The decrease in the amount of Cx43 in conjunction with the histological changes could represent the substrate for the atrial arrhythmias associated with AC.
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