title: Increased α-Actinin-2 Expression in the Atrial Myocardium of Patients with Atrial Fibrillation Related to Rheumatic Heart Disease.
abstract: OBJECTIVE
  Atrial ﬁbrosis, a marker of atrial structural remodeling, plays a critical role in atrial ﬁbrillation (AF). α- Actinin-2 is associated with structural remodeling related to stretching. The transforming growth factor-β1 (TGF-β1)/Smad pathway plays an important role in atrial fibrosis. We investigated the effects of the TGF-β1/Smad signaling pathway on α-actinin-2 in atrial fibrosis in patients with AF.
  
  
  METHODS
  Forty-one right atrial specimens obtained from patients with rheumatic heart disease (RHD) were divided into a chronic (c)AF group, i.e. RHD + cAF (n = 29), and a sinus rhythm group, i.e. RHD + sinus rhythm (n = 12). Patients with congenital heart disease (CHD) and sinus rhythm who underwent heart surgery served as controls (n = 10). Fibrosis was assessed by histological examination, and expression of α-actinin-2, TGF-β1 and Smad2/phosphorylated Smad2 (p-Smad2) was evaluated by immunohistochemistry, quantitative real-time PCR and Western blotting. In rat atrial fibroblasts treated with TGF-β1, the collagen content was measured using hydroxyproline detection, and α-actinin-2 and p-Smad2 were evaluated by semiquantitative reverse-transcription PCR and Western blotting.
  
  
  RESULTS
  The histology results revealed a significant increase in atrial fibrosis in AF patients. The collagen content, mRNA and protein expression levels of α-actinin-2 and the components of the TGF-β1/Smad signaling pathway were significantly gradually increased in the CHD + sinus rhythm, RHD + sinus rhythm and RHD + cAF groups (p < 0.05). The mRNA and protein levels of α-actinin-2 and TGF-β1 in RHD patients were positively correlated with the collagen volume fraction. A positive correlation between the expression of α-actinin-2 and TGF-β1 was also observed. In rat atrial fibroblasts treated with TGF-β1, the collagen content was greater than that in the control group (p < 0.05), and the expression levels of α- actinin-2 and p-Smad2 were also upregulated (p < 0.05).
  
  
  CONCLUSIONS
  α-Actinin-2 expression was increased in the atrial tissues of patients with AF secondary to RHD. α-Actinin-2 was upregulated via the TGF-β1/Smad pathway in atrial fibroblasts, which suggests that it may be involved in TGF-β1/Smad pathway-induced atrial fibrosis in patients with AF.
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Nan
authors.initials: N
authors.lastname: Zhang
authors.forename: Xuejiao
authors.initials: X
authors.lastname: Tang
authors.forename: Fajin
authors.initials: F
authors.lastname: Liu
authors.forename: Suxin
authors.initials: S
authors.lastname: Luo
authors.forename: Hua
authors.initials: H
authors.lastname: Xiao
mesh_terms: D000185:Actinin / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001281:Atrial Fibrillation / Q000209:etiology / Q000378:metabolism*; D015153:Blotting, Western; D002478:Cells, Cultured; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006325:Heart Atria / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D053858:Metabolic Networks and Pathways; D008854:Microscopy, Electron; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D012214:Rheumatic Heart Disease / Q000150:complications*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C401401:ACTN2 protein, human; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; D000185:Actinin