As part of the CBAC Seminar series, join us for this presentation by Toon van Veen, Associate Professor, Department of Medical Physiology at the University Medical Centre Utrecht, The Netherlands.
This seminar will be virtual. Register for this event by going here.
Seminar Title: "Arrhythmogenic cardiomyopathy: from bedside to bench and back to the patient"
Abstract: Arrhythmogenic cardiomyopathy (ACM), also known as arrhythmogenic right ventricular cardiomyopathy (ARVC), is a progressive inheritable cardiac disease which is characterized by a gradual fibrofatty replacement of cardiomyocytes in the ventricles. Pathogenic variants that trigger onset of the disease are primarily found in genes encoding proteins that constitute the desmosomes, such as plakophilin-2 (PKP2), plakoglobin (JUP), desmoplakin (DSP), desmoglein-2 (DSG2) and desmocollin-2 (DSC2), but also in non-desmosomal genes such as phospholamban (PLN). Presentation of ACM (prevalence estimated to be around 1:1000 – 1:5000) mostly occurs in adolescence, often between the second and fourth decade of life, however presentation is age and sex dependent and therefore highly variable among patients. Individuals with ACM suffer from an increased risk of ventricular arrhythmias and sudden cardiac death (SCD), often occurring in young adults during exercise, in early (asymptomatic) stages of the disease. However, disease penetrance is incomplete, and imaging techniques are at present unable to detect subclinical stages of the disease, making early detection of ACM to prevent SCD challenging. A better understanding of the mechanisms underlying ACM is needed to identify markers of early disease and predict potential arrhythmic events.
In the past decade, several experimental models have been developed that recapitulate clinical characteristics of this life-threatening disease. Studying those models has provided new insights in the molecular mechanisms that steer onset and progression of ACM. Amongst those findings we uncovered a potential leading role for dysregulation of the calcium homeostasis at the early onset of diseases presentation, subsequently leading to contractile impairment and an increased vulnerability for arrhythmias. Application of computational modeling allowed to further dissect the consequences of alterations in the individual contributors to calcium homeostasis and allowed to translate findings from experimental models to the situation in patients. Regarding the aspect of early detection of patients being at risk for disease onset, or to monitor progression of severity, we explored the potency of several new biomarkers.
In this presentation, I will discuss the clinical manifestation of ACM, the experimental findings that we obtained in the last couple of years and how they might contribute to improvements in disease management.
For more information, contact Huyen (Gwen) Nguyen at email@example.com
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