title: Atrial tissue expression of receptor for advanced glycation end-products (RAGE) and atrial fibrosis in patients with mitral valve disease.
abstract: BACKGROUND
  It has been reported that receptor for advanced glycation end-products (RAGE) plays a significant role in cardiac fibrosis. Nonetheless, the precise relationship between the RAGE and atrial fibrosis has never been studied in humans. The aim of this study was to determine whether degree of atrial fibrosis was associated with atrial tissue expression of RAGE in patients with mitral valve disease (MVD).
  
  
  METHODS
  We collected human left atrial (LA) appendage tissue from 25 patients who underwent mitral valve surgery. We quantified the expression of RAGE and other protein markers by Western blotting and compared these levels with histological evaluations.
  
  
  RESULTS
  RAGE expression in the LA appendage tissue was significantly correlated with atrial fibrosis (r=0.681, p=0.001). RAGE expression (regression coefficient [B] 9.49, 95% confidence interval [CI] 4.76-14.2, p<0.001) and LA diameter (B 0.43, 95% CI 0.13-0.74, p=0.008) were independently associated with degree of atrial fibrosis in multiple linear regression analysis. RAGE expression was significantly correlated with protein expression of von Willebrand factor (r=0.659, p<0.001), vascular endothelial cadherin (r=0.757, p<0.001), ICAM-1 (r=0.568, p=0.003), and PECAM-1 (r=0.423, p=0.035) in the LA appendage tissue. In addition, patients with severe mitral stenosis (MS) had higher atrial RAGE expression than those with no, mild, or moderate MS (p=0.013). Patients with MVD and atrial fibrillation (AF) had more severe atrial fibrosis (p=0.024) and higher RAGE expression (p=0.047) than those who remained in sinus rhythm.
  
  
  CONCLUSIONS
  Atrial tissue expression of RAGE was significantly associated with atrial fibrosis, severe MS, and AF rhythm in patients with MVD.
authors.affiliation: Yonsei University Health System, Seoul, Republic of Korea.
authors.forename: Pil-Sung
authors.initials: PS
authors.lastname: Yang
authors.affiliation: Yonsei University Health System, Seoul, Republic of Korea.
authors.forename: Seung Hyun
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Ewha Womans University, Seoul, Republic of Korea.
authors.forename: Junbeom
authors.initials: J
authors.lastname: Park
authors.affiliation: Yonsei University Health System, Seoul, Republic of Korea.
authors.forename: Tae-Hoon
authors.initials: TH
authors.lastname: Kim
authors.affiliation: Yonsei University Health System, Seoul, Republic of Korea.
authors.forename: Jae-Sun
authors.initials: JS
authors.lastname: Uhm
authors.affiliation: Yonsei University Health System, Seoul, Republic of Korea.
authors.forename: Boyoung
authors.initials: B
authors.lastname: Joung
authors.affiliation: Yonsei University Health System, Seoul, Republic of Korea.
authors.forename: Moon-Hyoung
authors.initials: MH
authors.lastname: Lee
authors.affiliation: Yonsei University Health System, Seoul, Republic of Korea.
authors.forename: Byung-Chul
authors.initials: BC
authors.lastname: Chang
authors.affiliation: Yonsei University Health System, Seoul, Republic of Korea. Electronic address: hnpak@yuhs.ac.
authors.forename: Hui-Nam
authors.initials: HN
authors.lastname: Pak
mesh_terms: D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D005355:Fibrosis / Q000000981:diagnostic imaging / Q000378:metabolism; D015870:Gene Expression; D006325:Heart Atria / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020928:Mitogen-Activated Protein Kinases / Q000096:biosynthesis* / Q000235:genetics; D008944:Mitral Valve Insufficiency / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*
chemical_list: D000951:Antigens, Neoplasm; C498978:MOK protein, human; D020928:Mitogen-Activated Protein Kinases
keywords: Atrial fibrillation; Atrial fibrosis; Mitral valve disease; RAGE