Atrial Fibrillation Promotion in a Rat Model of Rheumatoid Arthritis.
Atrial Fibrillation Promotion in a Rat Model of Rheumatoid Arthritis.
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类风湿性关节炎大鼠模型中心房颤动的促进
DOI：
10.1161/jaha.117.007320
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发表时间：
2017-12-21
影响因子：
5.4
通讯作者：
Li Y
中科院分区：
文献类型：
--
作者：
Dai H;Wang X;Yin S;Zhang Y;Han Y;Yang N;Xu J;Sun L;Yuan Y;Sheng L;Gong Y;Li Y
背景：类风湿性关节炎（RA）患者中房颤（AF）的患病率明显较高，但其潜在机制仍知之甚少。本研究的目的是评估RA对AF易感性和RA大鼠模型心房致心律失常重构的影响。方法和结果通过用弗氏不完全佐剂中的II型胶原免疫在大鼠中诱导胶原诱导的关节炎。在发生关节炎的大鼠中，在初次免疫8周后检查了AF易感性和心房重构。胶原诱导性关节炎大鼠的AF诱导率和持续时间显著增加，AF持续时间与血清IL-6和TNF-α水平显著正相关。胶原诱导性关节炎大鼠的心房传导时间延长，心房有效不应期无变化。心房传导延迟伴随心房纤维化显著增加。此外，还观察到心房结构和自主性重构，包括左心房扩张、心房肌细胞凋亡和自噬以及心房异质性交感神经过度支配。有趣的是，我们发现胶原诱导的关节炎对连接蛋白、Nav1.5和心房中主要离子通道的蛋白表达没有显著影响。结论我们证明RA通过诱导AF促进心房重构增加AF易感性。这项研究可以提供对RA诱导的AF的潜在机制的见解，并验证适合进一步机制和治疗探索的模型。
Background The prevalence of atrial fibrillation (AF) is significantly higher in rheumatoid arthritis (RA) patients, but the underlying mechanisms remain poorly understood. The goal of this study was to assess the effects of RA on AF susceptibility and atrial arrhythmogenic remodeling in a rat model of RA. Methods and Results Collagen‐induced arthritis was induced in rats by immunization with type II collagen in Freund's incomplete adjuvant. Among the rats that developed arthritis, AF susceptibility and atrial remodeling were examined 8 weeks after the primary immunization. AF inducibility and duration were substantially increased in collagen‐induced arthritis rats, and AF duration was significantly and positively correlated with the serum IL‐6 and TNF‐α levels. Rats with collagen‐induced arthritis showed prolonged atrial conduction time with no changes in the atrial effective refractory period. Atrial conduction delay was accompanied by significantly increased atrial fibrosis. In addition, atrial structural and autonomic remodeling, including left atrial dilation, apoptosis and autophagy of atrial myocytes, and atrial heterogeneous sympathetic hyperinnervation, was observed. Interestingly, we found that collagen‐induced arthritis had no significant effects on connexins, Nav1.5, and the main ion channels' protein expressions in atria. Conclusions We demonstrated that RA increased AF susceptibility by inducing AF‐promoting atrial remodeling. This study may provide insights into mechanisms underlying RA‐induced AF and validate a model that is suitable for further mechanistic and therapeutic exploration.