title: Upregulation of sestrins protect atriums against oxidative damage and fibrosis in human and experimental atrial fibrillation.
abstract: 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.
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Zengxiang
authors.initials: Z
authors.lastname: Dong
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Chaolan
authors.initials: C
authors.lastname: Lin
authors.affiliation: Intensive Care Unit, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Zhejiang, China.
authors.forename: Yujiao
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Laboratory of Physiology, Harbin Medical University, Harbin, China.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Jin
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Zhenjun
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Sun
authors.affiliation: Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Chengcheng
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Han
mesh_terms: D000804:Angiotensin II / Q000378:metabolism; D001281:Atrial Fibrillation / Q000209:etiology / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D015415:Biomarkers; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000235:genetics; D003094:Collagen / Q000378:metabolism; D015897:Comorbidity; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D005355:Fibrosis; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D006325:Heart Atria / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D006651:Histocytochemistry; D006801:Humans; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D015415:Biomarkers; D017382:Reactive Oxygen Species; D000804:Angiotensin II; D003094:Collagen; D002118:Calcium