CaMKII inhibition reduces isoproterenol-induced ischemia and arrhythmias in hypertrophic mice

• Published in: Oncotarget Vol. 8; no. 11; pp. 17504 - 17509
• Main Authors: Feng, Ying, Cheng, Jun, Wei, Baozhu, Wang, Yanggan
• Format: Journal Article
• Language: English
• Published: United States Impact Journals LLC 14-03-2017
• Subjects: Animals; Arrhythmias, Cardiac - chemically induced; Arrhythmias, Cardiac - enzymology; Arrhythmias, Cardiac - etiology; Calcium-Calmodulin-Dependent Protein Kinase Type 2 - antagonists & inhibitors; Cardiomegaly - complications; Cardiomegaly - enzymology; Cardiotonic Agents - toxicity; Disease Models, Animal; Electrocardiography; Enzyme Inhibitors - pharmacology; Heart - drug effects; Isoproterenol - toxicity; Male; Mice; Mice, Inbred C57BL; Myocardial Ischemia - chemically induced; Myocardial Ischemia - enzymology; Research Paper: Pathology; adrenergic stimulation; Pathology Section; CaMKII; cardiac hypertrophy; arrhythmia
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.15099

The Ca/calmodulin-dependent protein kinase II (CaMKII), an arrhythmogenic molecule, is excessively activated in cardiac hypertrophy. Here, we investigated the effect of CaMKII inhibition in isoproterenol (ISO)-induced arrhythmias in hypertrophic mice.
ISO induced multiple types of arrhythmias in the hypertrophic mice but not in the normal mice. The QTc intervals were prolonged and the amplitudes of T waves were increased significantly by ISO prior to arrhythmia initiation. Inhibition of CaMKII prevented ISO-induced QTc prolongation and T wave elevation and abrogated arrhythmia induction.
Pressure-overload cardiac hypertrophy was induced in mice by thoracic aortic banding. Arrhythmias were recorded by electrocardiogram in conscious mice.
CaMKII inhibition is effective in suppressing adrenergic activation-induced ventricular arrhythmias in cardiac hypertrophy, of which the ventricular ischemia-induced CaMKII activation plays an important role.