Upregulation of sestrins protect atriums against oxidative damage and fibrosis in human and experimental atrial fibrillation.
Upregulation of sestrins protect atriums against oxidative damage and fibrosis in human and experimental atrial fibrillation.
复制标题
上调 sestrins 可保护心房免受人类和实验性心房颤动的氧化损伤和纤维化
DOI：
10.1038/srep46307
复制
发表时间：
2017-04-11
影响因子：
4.6
通讯作者：
Han W
中科院分区：
文献类型：
--
作者：
Dong Z;Lin C;Liu Y;Jin H;Wu H;Li Z;Sun L;Zhang L;Hu X;Wei Y;Wang C;Han W
房颤（AF）在老年人中很常见，已建议使用Sestrin（Sesns）预防与年龄相关的病理。本研究的目的是探讨Sesns在AF中的作用。收集临床数据，并从接受瓣膜修复的患者中获得小样本的心耳和心房。Sesn 1、Sesn 2和Sesn 3在永久性房颤（PmAF）患者中的表达显著高于窦性心律（SR）患者，且在PmAF患者中左心房的表达进一步高于右心房。超氧阴离子和丙二醛含量增加，并与Sesn 1/2/3蛋白表达呈正相关。在培养的HL-1细胞中，过表达Sesns 1/2/3可显著降低活性氧（ROS）的产生和钙超载，并提高细胞存活率。相反，敲低Sesn 1/2/3导致ROS和Ca 2+超载显著增加。此外，Sesn 1/2的过表达显著降低了成纤维细胞的增殖，以及降低了血管紧张素II刺激的心脏成纤维细胞中胶原和纤连蛋白1的蛋白表达。我们的研究首次证明，Sesns表达在AF中显著上调，因此可能保护心脏免受氧化损伤和心房纤维化。
Atrial Fibrillation (AF) is common in the elderly and Sestrins (Sesns) have been suggested to prevent age-related pathologies. The aim of this study was to investigate the effects of Sesns in AF. Clinical data were collected and a small sample of atrial appendage and atrium was obtained from patients undergoing valve repairment. The expression of Sesn1, Sesn2, and Sesn3 was significantly higher in patients with permanent atrial fibrillation (PmAF) than that in sinus rhythm (SR), and further greater in the left atrium than the right in PmAF patients. Superoxide anion and malondialdehyde were enhanced and positively correlated to the protein expression of Sesn1/2/3. Reactive oxygen species (ROS) production and Ca2+overload were significantly decreased and cell survival was enhanced by overexpression of Sesns 1/2/3 in cultured HL-1 cells. Conversely, knockdown of Sesn1/2/3 resulted in significantly increased ROS and Ca2+overload. In addition, the overexpression of Sesn1/2 significantly reduced the proliferation of fibroblasts, as well as decreased the protein expression of collagen and fibronectin1 in angiotensin II-stimulated cardiac fibroblasts. Our study demonstrated for the first time that Sesns expression is significantly up-regulated in AF, which therefore may protect hearts against oxidative damage and atrial fibrosis.