The role of Intercalated discs in cardiomyopathy mice model

Doctoral Dissertation uoadl:2923827 159 Read counter

Unit:
Faculty of Medicine
Library of the School of Health Sciences
Deposit date:
2020-10-01
Year:
2020
Author:
Athanasiadis Nikolaos
Dissertation committee:
Νικόλαος Καβαντζάς, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Ευστράτιος Πατσούρης, Ομότιμος Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Κωνσταντίνος Δάβος, Ερευνητής Β', Κέντρο Κλινικής Πειραματικής Χειρουργικής και Μεταφραστικής Έρευνας, ΙΙΒΕΑΑ
Ανδρέας Λάζαρης, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Δημήτριος Χανιώτης, Καθηγητής, Τμήμα Βιοιατρικών Επιστημών, ΠΑΔΑ
Εμμανουήλ Μαυροειδής, Ερευνητής Γ', Κέντρο Βασικής Έρευνας, ΙΙΒΕΑΑ
Ειρήνη Θυμαρά, Επίκουρη Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Original Title:
Ο ρόλος των ενδιάμεσων ινιδίων σε μύες με μυοκαρδιοπάθεια
Languages:
Greek
Translated title:
The role of Intercalated discs in cardiomyopathy mice model
Summary:
Aims: The role of intercalated disc (ID)-related proteins in the structure and function of ventricular myocardium has been studied extensively, but their role in the cardiac conduction system remains elusive. Our objective was to investigate the effect of alterations of ID-related proteins on the structure and function of the cardiac conduction system and their implication in arrhythmogenesis in arrhythmogenic cardiomyopathy (ACM).
Methods and results: Studying mice and human cardiac samples, we observed that the atrial pacemaker complex exhibits high amounts of desmin and desmoplakin, in structures we call “lateral IDs”. We used desmin-deficient (Des-/-) mice as an ACM model. In SAN from Des-/- mice, these “lateral IDs” were diminished, and electrophysiological recordings revealed increased pacemaker potential and higher diastolic depolarization rate compared to wild-type (WT) mice. Prolonged interatrial conduction was also observed in Des-/- mice. Upregulation of ICaT channel, Cav3.1 in the Des-/- myocardium and a reduction of the funny channel HCN1 could underlie these functional differences. To investigate arrhythmogenicity, electrocardiographic analysis of desmin-deficient mice revealed a major increase in supraventricular and ventricular ectopic beats compared to WT. Heart rate variability analysis indicates a sympathetic predominance on sinoatrial node in Des-/- mice, which may further contribute to arrhythmogenicity.
Conclusions: Our results indicate that the conduction system may be involved in ACM arrhythmogenesis through structural and functional abnormalities of the atrial pacemaker complex. These alterations may be enhanced by the sympathetic component of the cardiac autonomic nervous system, thus leading to increased arrhythmogenesis.
Main subject category:
Health Sciences
Keywords:
Arrhythmogenic cardiomyopathy; intercalated discs; desmin; heart rate variability; desmosomArrhythmogenic cardiomyopathy; intercalated discs; desmin; heart rate variability; animal models; cytoskeleton; electron microscopy.
Index:
No
Number of index pages:
0
Contains images:
Yes
Number of references:
254
Number of pages:
144
File:
File access is restricted only to the intranet of UoA.

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