Dedifferentiation of atrial cardiomyocytes as a result of chronic atrial fibrillation.
Chronic atrial fibrillation was induced in goats by electrical pacing. After 9 to 23 weeks of sustained atrial fibrillation, the morphology of the atrial structures was examined. The majority of the cardiomyocytes exhibited marked changes in their cellular substructures, with the replacement of sarcomeres by glycogen as the main characteristic. Using immuno-histochemical staining procedures, we assessed the expression and organization of contractile and cytoskeletal proteins in these cases and compared them with the expression and organization of these proteins in normal atria. Part of the atrial cardiomyocytes acquired a dedifferentiated phenotype, as deduced from the re-expression of alpha-smooth muscle actin, the disappearance of cardiotin, and the staining patterns of titin, which resembled those of embryonic cardiomyocytes. From these results we conclude that chronic atrial fibrillation induces myocardial dedifferentiation. This model of chronic atrial fibrillation in goats offers the possibility to study the time course of changes in cardiac structure during sustained atrial fibrillation and after cardioversion.
Ausma
J
J
Department of Molecular Cell Biology and Genetics, Cardiovascular Research Institute Maastricht, Maastricht University, The Netherlands.
Wijffels
M
M
van Eys
G
G
Koide
M
M
Ramaekers
F
F
Allessie
M
M
Borgers
M
M
D000818:Animals; D001281:Atrial Fibrillation / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D015415:Biomarkers; D002304:Cardiac Pacing, Artificial / Q000009:adverse effects; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002454:Cell Differentiation; D002467:Cell Nucleus; D002908:Chronic Disease; D064211:Connectin; D003285:Contractile Proteins / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism; D005260:Female; D006041:Goats; D006325:Heart Atria / Q000378:metabolism / Q000473:pathology*; D007150:Immunohistochemistry; D009124:Muscle Proteins / Q000378:metabolism; D009130:Muscle, Smooth / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D011494:Protein Kinases / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000378:metabolism
D015415:Biomarkers; D015815:Cell Adhesion Molecules; D064211:Connectin; D003285:Contractile Proteins; D003598:Cytoskeletal Proteins; D009124:Muscle Proteins; D011494:Protein Kinases