Upregulation of sestrins protect atriums against oxidative damage and fibrosis in human and experimental atrial fibrillation

• Published in: Scientific reports 2017-04, Vol.7 (1), p.46307-46307, Article 46307
• Main Authors: Dong, Zengxiang, Lin, Chaolan, Liu, Yujiao, Jin, Hongbo, Wu, Hong, Li, Zhenjun, Sun, Liping, Zhang, Lu, Hu, Xi, Wei, Yingying, Wang, Chengcheng, Han, Wei
• Format: Article
• Language: English
• Subjects: 692/4019/592; 692/699/75/29/1309; 82/80; 96/2; 96/31; Age; Angiotensin; Angiotensin II; Angiotensin II - metabolism; Atrial Fibrillation - etiology; Atrial Fibrillation - metabolism; Atrial Fibrillation - pathology; Atrial Fibrillation - physiopathology; Atrium; Biomarkers; Calcium; Calcium - metabolism; Cardiac arrhythmia; Cell Line; Cell survival; Cell Survival - genetics; Collagen; Collagen - metabolism; Comorbidity; Female; Fibrillation; Fibroblasts; Fibroblasts - metabolism; Fibrosis; Gene Expression Regulation; Gene Knockdown Techniques; Geriatrics; Heart Atria - metabolism; Heart Atria - pathology; Heart Atria - physiopathology; Heart diseases; Histocytochemistry; Humanities and Social Sciences; Humans; Male; Malondialdehyde; Middle Aged; multidisciplinary; Oxidative Stress; Protein expression; Reactive oxygen species; Reactive Oxygen Species - metabolism; Science; Sinus; Superoxide
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep46307

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 Ca 2+ 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 Ca 2+ 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.