title: Simvastatin modulates remodeling of Kv4.3 expression in rat hypertrophied cardiomyocytes.
abstract: OBJECTIVE
  Hypertrophy has been shown to be associated with arrhythmias which can be caused by abnormal remodeling of the Kv4-family of transient potassium channels. Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase (statins) have recently been shown to exert pleiotropic protective effects in cardiovascular diseases, including anti-arrhythmias. It is hypothesized that remodeling of Kv4.3 occurs in rat hypertrophied cardiomyocytes and is regulated by simvastatin.
  
  
  METHODS
  Male Sprague-Dawley rats and neonatal rat ventricular myocytes (NRVMs) underwent abdominal aortic banding (AAB) for 7 weeks and angiotensin II (AngII) treatment, respectively, to induce cardiac hypertrophy. Kv4.3 expression by NRVMs and myocardium (subepicardial and subendocardial) in the left ventricle was measured. The transient outward potassium current (I(to)) of NRVMs was recorded using a whole-cell patch-clamp method.
  
  
  RESULTS
  Expression of the Kv4.3 transcript and protein was significantly reduced in myocardium (subepicardial and subendocardial) in the left ventricle and in NRVMs. Simvastatin partially prevented the reduction of Kv4.3 expression in NRVMs and subepicardial myocardium but not in the subendocardial myocardium. Hypertrophied NRVMs exhibited a significant reduction in the I(to) current and this effect was partially reversed by simvastatin.
  
  
  CONCLUSIONS
  Simvastatin alleviated the reduction of Kv4.3 expression, I(to) currents in hypertrophied NRVMs and alleviated the reduced Kv4.3 expression in subepicardial myocardium from the hypertrophied left ventricle. It can be speculated that among the pleiotropic effects of simvastatin, the anti-arrhythmia effect is partly mediated by its effect on Kv4.3.
authors.affiliation: Department of Cardiology, Tangdu Hospital, Fourth Military Medical University, Xi'an, China. sufeifei@fmmu.edu.cn
authors.forename: Feifei
authors.initials: F
authors.lastname: Su
authors.forename: Miaoqian
authors.initials: M
authors.lastname: Shi
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Yan
authors.forename: Dongbo
authors.initials: D
authors.lastname: Ou
authors.forename: Juntang
authors.initials: J
authors.lastname: Li
authors.forename: Zifan
authors.initials: Z
authors.lastname: Lu
authors.forename: Qiangsun
authors.initials: Q
authors.lastname: Zheng
mesh_terms: D000818:Animals; D019703:Calcineurin / Q000378:metabolism; D006332:Cardiomegaly / Q000188:drug therapy / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D051672:Shal Potassium Channels / Q000235:genetics / Q000378:metabolism*; D019821:Simvastatin / Q000494:pharmacology*
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D051672:Shal Potassium Channels; D019821:Simvastatin; D019703:Calcineurin