title: Fibrosis of the left atria during progression of heart failure is associated with increased matrix metalloproteinases in the rat.
abstract: OBJECTIVE
  The purpose of this study was to determine the pathogenic factors and molecular mechanisms involved in fibrosis of the atria.
  
  
  BACKGROUND
  Fibrosis is an important component of the pathophysiology of atrial fibrillation, especially when the arrhythmia is associated with heart failure (HF) or atrial dilation.
  
  
  METHODS
  We used a rat model of myocardial infarction (MI) complicated by various degrees of left ventricular dysfunction and atrial dilation to study fibrosis and matrix metalloproteinase (MMP) activity in the left atrial (LA) myocardium by means of histologic, Western blot, zymographic, and immunohistologic techniques.
  
  
  RESULTS
  Three months after surgical ligature of the left coronary artery, 27 rats had a large MI, 12 were in mild HF, and 15 in severe HF. Both groups had LA enlargement at the echocardiography. Masson's trichrome and picrosirius staining of tissue sections revealed marked fibrosis at the periphery of trabeculae and also surrounding myolytic myocytes, in both mild and severe HF. In mild HF, the activity and expression of the matrilysin MMP-7 were increased (122%), whereas in severe HF, both MMP-7 (211%) and the gelatinase MMP-2 (187%) were up-regulated. There were no changes in the expression or activity of MMP inhibitors, TIMP-1, -2, and -4. Immunostaining of cryosections showed that MMP-2 was present in the interstitial spaces, whereas MMP-7 accumulated in myolytic myocytes.
  
  
  CONCLUSIONS
  Hemodynamic overload of the atria is an important pathogenic factor of fibrosis; MMP-7 appears to be involved in the early stage of this tissue remodeling process.
authors.affiliation: INSERM Unité 460, Paris, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Boixel
authors.forename: Vincent
authors.initials: V
authors.lastname: Fontaine
authors.forename: Catherine
authors.initials: C
authors.lastname: Rücker-Martin
authors.forename: Paul
authors.initials: P
authors.lastname: Milliez
authors.forename: Liliane
authors.initials: L
authors.lastname: Louedec
authors.forename: Jean Baptiste
authors.initials: JB
authors.lastname: Michel
authors.forename: Marie Paule
authors.initials: MP
authors.lastname: Jacob
authors.forename: Stéphane N
authors.initials: SN
authors.lastname: Hatem
mesh_terms: D000818:Animals; D001281:Atrial Fibrillation / Q000209:etiology; D016275:Atrial Function; D015153:Blotting, Western; D017364:Collagenases / Q000032:analysis / Q000502:physiology; D004195:Disease Models, Animal; D018450:Disease Progression; D004452:Echocardiography; D005355:Fibrosis; D006325:Heart Atria / Q000737:chemistry* / Q000473:pathology*; D006333:Heart Failure / Q000150:complications / Q000473:pathology* / Q000503:physiopathology; D006439:Hemodynamics; D007150:Immunohistochemistry; D008297:Male; D053509:Matrix Metalloproteinase 13; D020778:Matrix Metalloproteinase 2 / Q000032:analysis / Q000502:physiology; D020783:Matrix Metalloproteinase 7 / Q000032:analysis / Q000502:physiology; D020782:Matrix Metalloproteinases / Q000032:analysis* / Q000502:physiology*; D009203:Myocardial Infarction / Q000150:complications / Q000473:pathology* / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D012720:Severity of Illness Index; D015854:Up-Regulation; D018487:Ventricular Dysfunction, Left / Q000150:complications / Q000473:pathology* / Q000503:physiopathology
chemical_list: D017364:Collagenases; D053509:Matrix Metalloproteinase 13; D020782:Matrix Metalloproteinases; C507083:Mmp13 protein, rat; D020783:Matrix Metalloproteinase 7; D020778:Matrix Metalloproteinase 2