CaMKII inhibition protects against hyperthyroid arrhythmias and adverse myocardial remodeling.

Hyperthyroidism can potentiate arrhythmias and cardiac hypertrophy, whereas Ca2+/calmodulin-dependent kinase II (CaMKII) promotes maladaptive myocardial remodeling. However, it remains unclear whether CaMKII contributes to the progression of hyperthyroid heart disease (HHD). This study demonstrated that CaMKII inhibition can relieve adverse myocardial remodeling and reduce sinus tachycardia, isoproterenol-induced atrial fibrillation, and ventricular arrhythmias in hyperthyroid mice with preserved heart function. Hyperthyroid cardiac hypertrophy was promoted by CaMKII upregulation-induced HDAC4/MEF2a activation. Briefly, CaMKII inhibition benefits HHD management greatly in mice by preventing arrhythmias and maladaptive remodeling. • Hyperthyroid heart disease (HHD) was developed in mice by T4 administration. • HHD was characterized by tachyarrhythmias and adverse myocardial remodeling. • T4 promoted CaMKII expression to derepress HDAC4/MEF2a for HHD progression. • CaMKII inhibition ameliorated HHD greatly and is a promising treatment target. [ABSTRACT FROM AUTHOR]