期刊
NATURE MEDICINE
卷 16, 期 4, 页码 470-U19出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nm.2124
关键词
-
资金
- Deutsche Forschungsgemeinschaft [BA 1870/3-2, BA 1870/7-1, Ru 1472/1-1, SFB-TR19]
- US National Institutes of Health [P01 HL076491-055328, P01 HL087018-02001]
- Deutsche Herzstiftung
- Werner Otto Stiftung
Observational clinical and ex vivo studies have established a strong association between atrial fibrillation and inflammation(1). However, whether inflammation is the cause or the consequence of atrial fibrillation and which specific inflammatory mediators may increase the atria's susceptibility to fibrillation remain elusive. Here we provide experimental and clinical evidence for the mechanistic involvement of myeloperoxidase (MPO), a heme enzyme abundantly expressed by neutrophils, in the pathophysiology of atrial fibrillation. MPO-deficient mice pretreated with angiotensin II (AngII) to provoke leukocyte activation showed lower atrial tissue abundance of the MPO product 3-chlorotyrosine, reduced activity of matrix metalloproteinases and blunted atrial fibrosis as compared to wild-type mice. Upon right atrial electrophysiological stimulation, MPO-deficient mice were protected from atrial fibrillation, which was reversed when MPO was restored. Humans with atrial fibrillation had higher plasma concentrations of MPO and a larger MPO burden in right atrial tissue as compared to individuals devoid of atrial fibrillation. In the atria, MPO colocalized with markedly increased formation of 3-chlorotyrosine. Our data demonstrate that MPO is a crucial prerequisite for structural remodeling of the myocardium, leading to an increased vulnerability to atrial fibrillation.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据