title: [Clinical on molecular basis of atrial fibrosis in patients with atrial fibrillation investigation].
abstract: OBJECTIVE
  To determine the molecular mechanisms involved in atrial fibrosis which occurs in patients with atrial fibrillation (AF) and to investigate their effects on the initiation and maintenance of AF.
  
  
  METHODS
  The right atrial tissue samples were taken from 73 patients with rheumatic heart disease who underwent heart valve replacement surgery. 34 patients had no history of AF (sinus rhythm group), 9 patients had paroxysmal AF and 30 patients had persistent AF. The mRNA content of collagen type I, collagen type III, MMP-2, TIMP-1, TIMP-2, TIMP-3 and TIMP-4 was measured by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and normalized to beta-actin or GAPDH.
  
  
  RESULTS
  Compared to sinus rhythm group, the mRNA of collagen type I and MMP-2 increased significantly in the persistent AF group (all, P < 0.01), followed by the paroxysmal AF group (all, P < 0.05). The mRNA of collagen type III was slightly higher in both AF groups than in the sinus rhythm group, but the differences were not statistically significant (P > 0.05). The mRNA of TIMP-1, TIMP-2 and TIMP-3 was down-regulated in the persistent AF group (all, P < 0.01, respectively), however, the trends of reduction did not reach statistical significance in the paroxysmal AF group (P > 0.05). The mRNA of TIMP-4 remained compatible in each group. The mRNA of collagen type I was significantly correlated with left atrial dimension (r = 0.336, P = 0.004) and AF duration (r = 0.339, P = 0.003). The mRNA of MMP-2 was significantly correlated with the mRNA of TIMP-2 (r = -0.326, P = 0.006), the mRNA of collagen type I (r = 0.322, P = 0.006), left atrial dimension (r = 0.300, P = 0.011) and AF duration (r = 0.300, P = 0.010).
  
  
  CONCLUSIONS
  The increased level of collagen type I associated with selective downregulation of TIMP-2 and upregulation of MMP-2 gene expression in atrium could be one of the molecular mechanisms of atrial fibrosis during atrial fibrillation, which correlates with the initiation and maintenance of AF.
authors.affiliation: Fujian Provincial Research Institute of Cardiovascular Diseases, Fuzhou 350001, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Ke
authors.forename: Chun-xuan
authors.initials: CX
authors.lastname: Xu
authors.forename: Ya-zhou
authors.initials: YZ
authors.lastname: Lin
authors.forename: Jian-cheng
authors.initials: JC
authors.lastname: Zhang
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.forename: Li-fang
authors.initials: LF
authors.lastname: Lin
authors.forename: Xi-zhong
authors.initials: XZ
authors.lastname: Hu
mesh_terms: D000293:Adolescent; D000328:Adult; D001281:Atrial Fibrillation / Q000378:metabolism / Q000473:pathology*; D024042:Collagen Type I / Q000235:genetics; D005260:Female; D005355:Fibrosis; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics; D008875:Middle Aged; D009206:Myocardium / Q000473:pathology*; D012333:RNA, Messenger / Q000032:analysis; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics; D019714:Tissue Inhibitor of Metalloproteinases / Q000235:genetics; D000097792:Tissue Inhibitor of Metalloproteinase-4
chemical_list: D024042:Collagen Type I; D020778:Matrix Metalloproteinase 2; D012333:RNA, Messenger; D019716:Tissue Inhibitor of Metalloproteinase-2; D019714:Tissue Inhibitor of Metalloproteinases; D000097792:Tissue Inhibitor of Metalloproteinase-4