title: Elevated expression of connective tissue growth factor in human atrial fibrillation and angiotensin II-treated cardiomyocytes.
abstract: BACKGROUND
  Atrial fibrosis is a feature of structural remodeling in atrial fibrillation (AF). Connective tissue growth factor (CTGF) is a potent profibrotic factor, but its role of CTGF in AF is not yet fully understood.
  
  
  RESULTS
  Right atrial appendages were obtained from 20 patients who underwent cardiac surgery (10 with sinus rhythm, 10 with AF). The mRNA level, protein level and immunohistochemical staining of CTGF were significantly increased in AF patients. In a porcine AF model, tissue angiotensin II (Ang II) and CTGF levels were significantly upregulated in both atria. In perfused rat hearts, Ang II stimulation increased CTGF expression, which could be inhibited by Ang II type I receptor antagonist. In a cell culture system, both atrial fibroblasts and myocytes were responsible for the increased CTGF expression under Ang II treatment. Ang II type I receptor antagonist could inhibit the Ang II-induced CTGF expression. Treating with recombinant CTGF, atrial fibroblasts expressed an increased level of collagen I. Furthermore, the CTGF level was highly correlated with tissue Ang II content in AF pigs.
  
  
  CONCLUSIONS
  AF patients and animals exhibited a significantly increased expression of CTGF. Ang II stimulation upregulated CTGF expression in both atrial fibroblasts and myocytes. Ang II-induced CTGF expression might be involved in atrial substrate remodeling.
authors.affiliation: Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taiwan.
authors.forename: Wen-Chin
authors.initials: WC
authors.lastname: Ko
authors.forename: Chuang-Ye
authors.initials: CY
authors.lastname: Hong
authors.forename: Shaw-Min
authors.initials: SM
authors.lastname: Hou
authors.forename: Chien-Huang
authors.initials: CH
authors.lastname: Lin
authors.forename: Eng-Thiam
authors.initials: ET
authors.lastname: Ong
authors.forename: Chwen-Fang
authors.initials: CF
authors.lastname: Lee
authors.forename: Chia-Ti
authors.initials: CT
authors.lastname: Tsai
authors.forename: Ling-Ping
authors.initials: LP
authors.lastname: Lai
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000804:Angiotensin II / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001281:Atrial Fibrillation / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D055513:Connective Tissue Growth Factor / Q000378:metabolism*; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006325:Heart Atria / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013552:Swine
chemical_list: D012333:RNA, Messenger; D000804:Angiotensin II; D055513:Connective Tissue Growth Factor; D003094:Collagen