Arrhythmias & electrophysiology
Integrin β1D Deficiency–Mediated RyR2 Dysfunction Contributes to Catecholamine-Sensitive Ventricular Tachycardia in Arrhythmogenic Right Ventricular Cardiomyopathy
Authors' conclusion
Our data suggest that integrin β1D deficiency represents a novel mechanism underlying the increased risk of ventricular arrhythmias in patients with ARVC.
Study context
- Population
- Patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) (LV tissue) and cardiac-specific integrin β1D knockout mice
- Comparison
- Integrin β1D deficiency vs normal β1D expression
Methodological detailscardiac-specific β1D knockout mouse model, protein mass spectrometry, lipid bilayer single channel recordings
- Cardiac-specific β1D knockout mouse model
- Protein mass spectrometry
- Lipid bilayer single channel recordings
Main finding
As reported in the abstract
- Integrin β1 downregulated in ARVC hearts without changes to Ca2+-handling proteins
- Integrin β1D deficiency and RyR2 Ser-2030 hyperphosphorylation in LV tissue from ARVC patients but not ischemic or hypertrophic cardiomyopathy
- Purified integrin β1D stabilised RyR2: decreased open probability and mean open time, increased mean close time
- β1D knockout mice: normal cardiac function and morphology but catecholamine-sensitive polymorphic VT, with increased RyR2 Ser-2030 phosphorylation and aberrant Ca2+ handling
- Loss of DSP induces integrin β1D deficiency in ARVC via an ERK1/2-fibronectin-ubiquitin/lysosome pathway
Original publication
Integrin β1D Deficiency–Mediated RyR2 Dysfunction Contributes to Catecholamine-Sensitive Ventricular Tachycardia in Arrhythmogenic Right Ventricular Cardiomyopathy. Circulation. Published 3 March 2020. doi:10.
Summarised from the published abstract; every number is checked against it