title: Angiotensin II-mediated up-regulation of connective tissue growth factor promotes atrial tissue fibrosis in the canine atrial fibrillation model.
abstract: OBJECTIVE
  Remodelling of the extracellular matrix (ECM) plays an important role in the production of arrhythmogenic substrate for atrial fibrillation (AF), and is considered to be promoted by the connective tissue growth factor (CTGF). Our objective was to assess the relationship between CTGF and ECM synthesis, and the effect of olmesartan on these processes.
  
  
  RESULTS
  Fifteen canine AF models were produced by rapid atrial stimulation. They were divided into three groups: pacing control (n = 5): 6-week pacing, pacing + olmesartan (n = 5): pacing with olmesartan (2 mg/kg/day), and non-pacing group (n = 5). In the pacing control group, messenger ribonucleic acid expressions of CTGF and collagen types 1 and 3 were up-regulated in comparison with the non-pacing group (P < 0.05) while transforming growth factor-β (TGF-β) did not exhibit a significant difference. In the pacing + olmesartan group, these up-regulations were suppressed (P < 0.05). In fluorescent immunostaining, the expression of CTGF was localized in the cytoplasm. The protein level of collagen type 3 was increased in the pacing control and it was suppressed in the pacing + olmesartan group.
  
  
  CONCLUSIONS
  CTGF and associated genes were up-regulated in the atria with the appearance of fibrosis. Because this up-regulation was independent of TGF-β and suppressed by olmesartan, CTGF up-regulation was considered to be mediated by angiotensin II.
authors.affiliation: Department of Cardio-Angiology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara 252-0374, Japan. dm07015u@st.kitasato-u.ac.jp
authors.forename: Michiro
authors.initials: M
authors.lastname: Kiryu
authors.forename: Shinichi
authors.initials: S
authors.lastname: Niwano
authors.forename: Hiroe
authors.initials: H
authors.lastname: Niwano
authors.forename: Jun
authors.initials: J
authors.lastname: Kishihara
authors.forename: Yuya
authors.initials: Y
authors.lastname: Aoyama
authors.forename: Hidehira
authors.initials: H
authors.lastname: Fukaya
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Masaki
authors.forename: Tohru
authors.initials: T
authors.lastname: Izumi
mesh_terms: D000804:Angiotensin II / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001281:Atrial Fibrillation / Q000378:metabolism*; D015153:Blotting, Western; D055513:Connective Tissue Growth Factor / Q000378:metabolism*; D004195:Disease Models, Animal; D004285:Dogs; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D006325:Heart Atria / Q000378:metabolism* / Q000503:physiopathology; D007093:Imidazoles / Q000494:pharmacology*; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D013777:Tetrazoles / Q000494:pharmacology*; D015854:Up-Regulation
chemical_list: D007093:Imidazoles; D013777:Tetrazoles; D000804:Angiotensin II; D055513:Connective Tissue Growth Factor; C437965:olmesartan