Treatment with IL-1 receptor antagonist significantly reduced ventricular tachycardia inducibility from 50% to 9.1% in a mouse model of type 2 diabetes.
Does inhibiting IL-1β, mitoROS, or SR Ca2+ leak reduce ventricular arrhythmia in Type 2 DM mice?
Cardiac IL-1β mediates diabetes-associated arrhythmia through mitoROS generation and enhanced SR Ca2+ leak, highlighting inflammation and calcium handling as potential therapeutic targets.
Absolute Event Rate: 9.1% vs 50%
p-value: p=0.042
Diabetes mellitus (DM) is associated with increased arrhythmia. Type 2 DM (T2DM) mice showed prolonged QT interval and increased ventricular arrhythmic inducibility, accompanied by elevated cardiac interleukin (IL)-1β, increased mitochondrial reactive oxygen species (mitoROS), and oxidation of the sarcoplasmic reticulum (SR) Ca2+ release channel (ryanodine receptor 2 RyR2). Inhibiting IL-1β and mitoROS reduced RyR2 oxidation and the ventricular arrhythmia in DM. Inhibiting SR Ca2+ leak by stabilizing the oxidized RyR2 channel reversed the diabetic arrhythmic risk. In conclusion, cardiac IL-1β mediated the DM-associated arrhythmia through mitoROS generation that enhances SR Ca2+ leak. The mechanistic link between inflammation and arrhythmias provides new therapeutic options.
Liu et al. (Fri,) conducted a other in Type 2 Diabetes Mellitus (T2DM) with arrhythmic risk (n=93). IL-1 receptor antagonist (IL-1RA) vs. Untreated DM mice was evaluated on Ventricular tachycardia (VT) inducibility (p=0.042). Treatment with IL-1 receptor antagonist significantly reduced ventricular tachycardia inducibility from 50% to 9.1% in a mouse model of type 2 diabetes.