Aliskiren protecting atrial structural remodeling from rapid atrial pacing in a canine model

作者：Zhao, Zhiqiang; Chen, Yan; Li, Weimin; Wang, Xinghua; Li, Jian; Yang, Wansong; Cheng, Lijun; Liu, Tong; Liu, Enzhao; Li, Guangping^*

来源：Naunyn-Schmiedebergs Archives of Pharmacology, 2016, 389(8): 863-871.

DOI：10.1007/s00210-016-1249-z

• Atrial fibrillation
• Aliskiren
• Structural remodeling
• Rapid atrial pacing

Atrial fibrillation (AF) contributing to the increasing mortality risk is the most common disease in clinical practice. Owing to the side effects and relative inefficacy of current antiarrhythmic drugs, some research focuses on renin-angiotensin-aldosterone system (RAS) for finding out the new treatment of AF. The purpose of this study is to confirm whether aliskiren as a proximal inhibitor of renin, which completely inhibits RAS, has beneficial effects on atrial structural remodeling in AF. In this study, rapid atrial pacing was induced at 500 beats per minute for 2 weeks in a canine model. A different dose of aliskiren was given orally for 2 weeks before rapid atrial pacing. HE staining and Masson's staining were used for analysis of myocardial fibrosis. TGF-beta 1, signal pathways, and pro-inflammatory cytokines were shown for the mechanism of structural remodeling after the treatment of aliskiren. Serious atrial fibrosis was induced by rapid atrial pacing, followed by the elevated TGF-beta 1, upregulated MEK and ERK1/2, and increased inflammatory factors. Aliskiren could apparently improve myocardial fibrosis by reducing the expression of TGF-beta 1, inhibiting MEK and ERK1/2 signal pathways, and decreasing IL-18 and TLR4 in both serum and atrial tissue. In conclusion, aliskiren could prevent atrial structural remodeling from rapid atrial pacing for 2 weeks. Aliskiren may play a potential beneficial role in the treatment of AF induced by rapid atrial pacing.

• 出版日期2016-8
• 单位天津市胸科医院; 天津医科大学