title: Calreticulin overexpression correlates with integrin-α5 and transforming growth factor-β1 expression in the atria of patients with rheumatic valvular disease and atrial fibrillation.
abstract: OBJECTIVE
  The aim of this study was to determine whether altered calreticulin expression and distribution contribute to the pathogenesis of atrial fibrillation (AF) associated with valvular heart disease (VHD).
  
  
  BACKGROUND
  AF affects electrophysiological and structural changes that exacerbate AF. Atrial remodeling reportedly underlies AF generation, but the precise mechanism of atrial remodeling in AF remains unclear.
  
  
  METHODS
  Right and left atrial specimens were obtained from 68 patients undergoing valve replacement surgery. The patients were divided into sinus rhythm (SR; n=25), paroxysmal AF (PaAF; n=11), and persistent AF (PeAF; AF lasting >6 months; n=32) groups. Calreticulin, integrin-α5, and transforming growth factor-β1 (TGF-β1) mRNA and protein expression were measured. We also performed immunoprecipitation for calreticulin with either calcineurin B or integrin-α5.
  
  
  RESULTS
  Calreticulin, integrin-α5, and TGF-β1 mRNA and protein expression were increased in the AF groups, especially in the left atrium in patients with mitral valve disease. Calreticulin interacted with both calcineurin B and integrin-α5. Integrin-α5 expression correlated with TGF-β1 expression, while calreticulin expression correlated with integrin-α5 and TGF-β1 expression. Despite similar cardiac function classifications, calreticulin expression was greater in the PeAF group than in the SR group.
  
  
  CONCLUSIONS
  Calreticulin, integrin-α5, and TGF-β1 expression was increased in atrial tissue in patients with AF and was related to AF type, suggesting that calreticulin is involved in the pathogenesis of AF in VHD patients.
authors: Cardiothoracic Surgery Department, First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Jiangsu Province, Nanjing 210029, China.
authors: Fei
authors: F
authors: Zhao
authors: Shijiang
authors: S
authors: Zhang
authors: Yongfeng
authors: Y
authors: Shao
authors: Yanhu
authors: Y
authors: Wu
authors: Jianwei
authors: J
authors: Qin
authors: Yijiang
authors: Y
authors: Chen
authors: Liang
authors: L
authors: Chen
authors: Haitao
authors: H
authors: Gu
authors: Xiaowei
authors: X
authors: Wang
authors: Chenjun
authors: C
authors: Huang
authors: Wei
authors: W
authors: Zhang
mesh_terms: D000293:Adolescent; D000328:Adult; D001281:Atrial Fibrillation / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D015153:Blotting, Western; D037282:Calreticulin / Q000096:biosynthesis / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D005786:Gene Expression Regulation; D006325:Heart Atria / Q000378:metabolism* / Q000473:pathology; D006349:Heart Valve Diseases / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D039482:Integrin alpha5 / Q000096:biosynthesis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012214:Rheumatic Heart Disease / Q000150:complications / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis / Q000235:genetics*; D055815:Young Adult
chemical_list: D037282:Calreticulin; D039482:Integrin alpha5; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1
keywords: AF; Atrial fibrillation; Atrial fibrosis; CHD; Calreticulin; DVD; Human myocardium; Integrin-α5; MVD; PaAF; PeAF; SR; Transforming growth factor-β1; VHD; atrial fibrillation; congenital heart disease; double valvular disease (mitral and aortic valves); mitral valvular disease; paroxysmal atrial fibrillation; persistent atrial fibrillation; sinus rhythm; valvular heart disease