| Title | Long-term treatment with ivabradine in transgenic atrial fibrillation mice counteracts HCN channel overexpression |
| Authors | Wang Juan Yang Yan-Min Li Yang Zhu Jun Lian Hong Shao Xing-Hui Zhang Han Fu Yi-Cheng Zhang Lian-Feng |
| Affiliation | Emergency and Intensive Care Center, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China. Department of Cardiology, Chinese PLA General Hospital, Beijing, China. State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. Department of Geriatrics, Peking University Third Hospital, Beijing, China. Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. |
| Keywords | HCN nnels,Ivabradine,atrial fibrillation,funny current,transgenic mice |
| Issue Date | 2018 |
| Publisher | Journal of cardiovascular electrophysiology |
| Citation | Journal of cardiovascular electrophysiology. 2018. |
| Abstract | Recent studies demonstrated funny current (I f ) selective inhibitor ivabradine(IVA) exerts anti-arrhythmic effects in heart failure and myocardial ischemia. However, little is known regarding the effects of long-term IVA treatment on I f current and hyperpolarization-activated cyclic nucleotide gated (HCN) channel overexpression.We investigated both the I f current and HCN channel expression in wild-type (WT) mice and the transgenic AF mice (TG) (heart-specific overexpressing of (pro) renin receptor transgenic mice), and examined the effects of IVA on the I f current and HCN channel expression, and whether those effects were sufficient to prevent AF episode. Compared with WT mice, the I f current density (at -170 mV: TG, -39.6±4.6 pA/pF; WT, -26.9±3.0 pA/pF, p<0.001) and activation kinetics (V1/2 : TG, -109.45±1.35 mV; WT, -128.20±1.65 mV), as well as HCN2 and HCN4 mRNA expression, and HCN4 protein expression, were significantly increased in the atrial myocytes of TG mice. After 4 months of IVA treatment (7 mg/kg per day orally), The effects of IVA on TG AF mice were accompanied by the inhibition of upregulation of HCN2 and HCN4 protein expression in atrial tissue, then resulted in a uniform I f loss-of f unction. Furthermore, we observed that ivabradine significantly decreased the incidence of AF in the TG mice (41.2% in TG mice, 16.7% in TG+IVA mice, p<0.01).IVA reduced the incidence of AF in mice, and the anti-arrhythmic effects of IVA are not limited to heart rate reduction, as it partially counteracts HCN overexpression and reverses electrophysiological cardiac remodeling by attenuating I f gain-of-function. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved. |
| URI | http://hdl.handle.net/20.500.11897/528504 |
| ISSN | 1540-8167 |
| DOI | 10.1111/jce.13772 |
| Indexed | PubMed |
| Appears in Collections: | 第三医院 |
