title: Kcne2 deletion promotes atherosclerosis and diet-dependent sudden death.
abstract: Coronary artery disease (CAD) is the leading cause of death worldwide. An estimated half of cases involve genetic predisposition. Sequence variants in human KCNE2, which encodes a cardiac and epithelial K(+) channel β subunit, cause inherited cardiac arrhythmias. Unexpectedly, human KCNE2 polymorphisms also associate with predisposition to atherosclerosis, with unestablished causality or mechanisms. Here, we report that germline Kcne2 deletion promotes atherosclerosis in mice, overcoming the relative resistance of this species to plaque deposition. In female western diet-fed mice, Kcne2 deletion increased plaque deposition >6-fold and also caused premature ventricular complexes and sudden death. The data establish causality for the first example of ion channel-linked atherosclerosis, and demonstrate that the severity of Kcne2-linked cardiac arrhythmias is strongly diet-dependent.
authors: Bioelectricity Laboratory, Dept. of Pharmacology, Dept. of Physiology and Biophysics, School of Medicine, University of California, Irvine, CA, USA.
authors: Soo Min
authors: SM
authors: Lee
authors: Bioelectricity Laboratory, Dept. of Pharmacology, Dept. of Physiology and Biophysics, School of Medicine, University of California, Irvine, CA, USA.
authors: Dara
authors: D
authors: Nguyen
authors: Department of Anesthesiology and Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, 610041, People's Republic of China. Electronic address: zyhu@hotmail.com.
authors: Zhaoyang
authors: Z
authors: Hu
authors: Bioelectricity Laboratory, Dept. of Pharmacology, Dept. of Physiology and Biophysics, School of Medicine, University of California, Irvine, CA, USA. Electronic address: abbottg@uci.edu.
authors: Geoffrey W
authors: GW
authors: Abbott
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000235:genetics* / Q000503:physiopathology; D050197:Atherosclerosis / Q000235:genetics* / Q000503:physiopathology; D016757:Death, Sudden, Cardiac / Q000473:pathology; D004032:Diet; D020022:Genetic Predisposition to Disease; D005838:Genotype; D018095:Germ-Line Mutation; D006801:Humans; D051379:Mice; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics*; D017384:Sequence Deletion
chemical_list: C489620:Kcne2 protein, mouse; D024642:Potassium Channels, Voltage-Gated
keywords: Cardiac arrhythmia; Long QT syndrome; Potassium channel; Sudden cardiac death