title: MicroRNA29: a mechanistic contributor and potential biomarker in atrial fibrillation.
abstract: BACKGROUND
  Congestive heart failure (CHF) causes atrial fibrotic remodeling, a substrate for atrial fibrillation (AF) maintenance. MicroRNA29 (miR29) targets extracellular matrix proteins. In the present study, we examined miR29b changes in patients with AF and/or CHF and in a CHF-related AF animal model and assessed its potential role in controlling atrial fibrous tissue production.
  
  
  RESULTS
  Control dogs were compared with dogs subjected to ventricular tachypacing for 24 hours, 1 week, or 2 weeks to induce CHF. Atrial miR29b expression decreased within 24 hours in both whole atrial tissue and atrial fibroblasts (-87% and -92% versus control, respectively; p<0.001 for both) and remained decreased throughout the time course. Expression of miR29b extracellular matrix target genes collagen-1A1 (COL1A1), collagen-3A1 (COL3A1), and fibrillin increased significantly in CHF fibroblasts. Lentivirus-mediated miR29b knockdown in canine atrial fibroblasts (-68%; p<0.01) enhanced COL1A1, COL3A1, and fibrillin mRNA expression by 28% (p<0.01), 19% (p<0.05), and 20% (p<0.05), respectively, versus empty virus-infected fibroblasts and increased COL1A1 protein expression by 90% (p<0.05). In contrast, 3-fold overexpression of miR29b decreased COL1A1, COL3A1, and fibrillin mRNA by 65%, 62%, and 61% (all p<0.001), respectively, versus scrambled control and decreased COL1A1 protein by 60% (p<0.05). MiR29b plasma levels were decreased in patients with CHF or AF (by 53% and 54%, respectively; both p<0.001) and were further decreased in patients with both AF and CHF (by 84%; p<0.001). MiR29b expression was also reduced in the atria of chronic AF patients (by 54% versus sinus rhythm; p<0.05). Adenoassociated viral-mediated knockdown of miR29b in mice significantly increased atrial COL1A1 mRNA expression and cardiac tissue collagen content.
  
  
  CONCLUSIONS
  MiR29 likely plays a role in atrial fibrotic remodeling and may have value as a biomarker and/or therapeutic target.
authors: Montreal Heart Institute Research Center, 5000 Belanger St E, Montreal, Quebec, H1T 1C8, Canada.
authors: Kristin
authors: K
authors: Dawson
authors: Reza
authors: R
authors: Wakili
authors: Balázs
authors: B
authors: Ordög
authors: Sebastian
authors: S
authors: Clauss
authors: Yu
authors: Y
authors: Chen
authors: Yuki
authors: Y
authors: Iwasaki
authors: Niels
authors: N
authors: Voigt
authors: Xiao Yan
authors: XY
authors: Qi
authors: Moritz F
authors: MF
authors: Sinner
authors: Dobromir
authors: D
authors: Dobrev
authors: Stefan
authors: S
authors: Kääb
authors: Stanley
authors: S
authors: Nattel
mesh_terms: D000368:Aged; D000818:Animals; D001281:Atrial Fibrillation / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D015415:Biomarkers / Q000097:blood; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D005355:Fibrosis / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D006325:Heart Atria / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006333:Heart Failure / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D010138:Pacemaker, Artificial; D020257:Ventricular Remodeling / Q000235:genetics / Q000502:physiology
chemical_list: D015415:Biomarkers; C532045:MIRN29a microRNA, human; D035683:MicroRNAs