title: Myocardial cell death in fibrillating and dilated human right atria.
abstract: OBJECTIVE
  The aim of the present study was to determine if myocytes can die by apoptosis in fibrillating and dilated human atria.
  
  
  BACKGROUND
  The cellular remodeling that occurs during atrial fibrillation (AF) may reflect a degree of dedifferentiation of the atrial myocardium, a process that may be reversible.
  
  
  METHODS
  We examined human right atrial myocardium specimens (n = 50) for the presence of apoptotic myocytes. We used immunohistochemical and Western blotting analysis to examine the expression of a final effector of programmed cell death, caspase-3 (CASP-3) and of regulatory proteins from the BCL-2 family.
  
  
  RESULTS
  Sections from atria in AF contained a high percentage of large myocytes with a disrupted sarcomeric apparatus replaced by glycogen granules (64.4 +/- 6.3% vs. 12.2 +/- 5.8%). These abnormal myocytes, which also predominated in atria from hearts with decreased left ventricular ejection fraction (42.3 +/- 10.1%), contained large nuclei, most of which were TUNEL positive, indicating a degree of DNA breakage. None of these abnormal myocytes expressed the proliferative antigen Ki-67. A small percentage of the enlarged nuclei (4.2 +/- 0.8%) contained condensed chromatin and were strongly TUNEL positive. Both the pro- and activated forms of CASP-3 were detected in diseased myocardial samples, which also showed stronger CASP-3 expression than controls. Expression of the antiapoptotic BCL-2 protein was decreased in diseased atria, whereas that of the proapoptotic BAX protein remained unchanged.
  
  
  CONCLUSIONS
  In fibrillating and dilated atria, apoptotic death of myocytes with myolysis contributes to cellular remodeling, which may not be entirely reversible.
authors.affiliation: INSERM U408, Faculté de Médecine, Xavier Bichat, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Aimé-Sempé
authors.forename: T
authors.initials: T
authors.lastname: Folliguet
authors.forename: C
authors.initials: C
authors.lastname: Rücker-Martin
authors.forename: M
authors.initials: M
authors.lastname: Krajewska
authors.forename: S
authors.initials: S
authors.lastname: Krajewska
authors.forename: M
authors.initials: M
authors.lastname: Heimburger
authors.forename: M
authors.initials: M
authors.lastname: Aubier
authors.forename: J J
authors.initials: JJ
authors.lastname: Mercadier
authors.forename: J C
authors.initials: JC
authors.lastname: Reed
authors.forename: S N
authors.initials: SN
authors.lastname: Hatem
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000502:physiology; D001281:Atrial Fibrillation / Q000503:physiopathology*; D016275:Atrial Function; D015153:Blotting, Western; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D004587:Electrophoresis, Agar Gel; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D019394:Ki-67 Antigen / Q000302:isolation & purification; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000166:cytology* / Q000201:enzymology
chemical_list: D019394:Ki-67 Antigen; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases