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Published on: December 2, 2016
Simvastatin modulates remodeling of Kv4.3 expression in rat hypertrophied cardiomyocytes
Feifei Su1, Miaoqian Shi, Zhiqiang Yan
1Department of Cardiology, Tangdu Hospital, Fourth Military Medical University, Xi'an, China. sufeifei@fmmu.edu.cn
Insights
Simvastatin partially prevented reductions in Kv4.3 expression and potassium current in hypertrophied heart cells. This suggests simvastatin
Area of Science:
- Cardiovascular Science
- Molecular Cardiology
- Pharmacology
Background:
- Cardiac hypertrophy is linked to arrhythmias due to abnormal remodeling of Kv4-family transient potassium channels.
- Statins, like simvastatin, show protective cardiovascular effects, including anti-arrhythmic properties.
- The role of simvastatin in regulating Kv4.3 channel remodeling in hypertrophy is unclear.
Purpose of the Study:
- To investigate Kv4.3 channel remodeling in rat hypertrophied cardiomyocytes.
- To determine if simvastatin regulates Kv4.3 expression and function in cardiac hypertrophy.
- To explore the potential anti-arrhythmic mechanisms of simvastatin.
Main Methods:
- Cardiac hypertrophy was induced in rats via abdominal aortic banding (AAB) and in neonatal rat ventricular myocytes (NRVMs) with angiotensin II (AngII).
- Kv4.3 expression levels were measured in NRVMs and left ventricular myocardium.
- Whole-cell patch-clamp electrophysiology was used to record transient outward potassium currents (I(to)) in NRVMs.
Main Results:
- Kv4.3 transcript and protein expression were significantly reduced in hypertrophied myocardium and NRVMs.
- Simvastatin partially attenuated the reduction of Kv4.3 expression in NRVMs and subepicardial myocardium.
- Hypertrophied NRVMs showed reduced I(to) currents, which were partially reversed by simvastatin treatment.
Conclusions:
- Simvastatin partially preserves Kv4.3 expression and I(to) current function in hypertrophied cardiomyocytes.
- Simvastatin mitigates Kv4.3 downregulation in subepicardial regions of the hypertrophied left ventricle.
- The anti-arrhythmic effects of simvastatin may be partly mediated by its influence on Kv4.3 channels.
Objectives:
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.
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