Melanie Zwiener:
Cardiac phenotype characterization of heterozygous plakoglobin deficient mice via echocardiography and telemetry
The arrhythmogenic right ventricular disease (ARVC) is a heartmuscle disease of which we have insufficient knowledge about the etiology. It causes arrhythmias, heart failure and sudden cardiac death. It can be difficult to diagnose, which impedes the analysis of the molecular base. A change in the gene of plakoglobin results in a special type of ARVC (naxos disease). Plakoglobin is a cytoskeletal protein, which is present in desmosomes as well as in adherens junctions. The genetic inactivation leads to an embryonic lethal phenotype due to a dysfunction of the intercalated discs, which limits the heart stability. Experiments were conducted on mice in order to investigate electrophysiological and functional impact of plakoglobin deficiency.
These experiments included electro- and echocardiographic studies as well as enhanced β-adrenergic stimulation (medicamentous or with endurance training). 12-channel-surface-ECGs were carried out on adult mice under different narcosis, while long-term ECGs were realized using telemetric transmitter implants on freely moving and physically stressed adult mice. Age- and training-related echocardiographic and electrocardiographic examination series were conducted.
Heterozygote plakoglobin deficiency results in an age-depending right ventricular dilatation, which training can accelerate. A reduced contractility shows after β-adrenergic stimulation of trained mice. Older and trained mice reveal an increased predisposition to arrhythmia; furthermore β1-stimulation increases the risk. A multifactorial interaction of myocardial stretch (with enhanced strain forces of the right ventricle), cytoskeletal changes and a functional conduction defect/ autonome dysbalance could lead to apoptotic action and in addition to myocardial atrophy.
These factors result in heart failure and arrhythmia.
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