Structural remodelling during chronic atrial fibrillation: act of programmed cell survival.
Atrial fibrillation is the most common cardiac arrhythmia with an overall prevalence of almost 1%. Increasing prevalence and associated risks such as stroke and mortality have increased the need for better and more reliable therapeutic treatment. This has stimulated research to elucidate the pathophysiological mechanisms underlying atrial fibrillation. Atrial fibrillation is primarily characterised by electrical remodelling and functional deterioration. Both phenomena are reversible but after prolonged duration of atrial fibrillation, a discrepancy occurs between rapid electrical remodelling and slow recovery of contractile function. Recent studies have indicated that morphological remodelling might underlie this incongruity. In experimental models of lone atrial fibrillation, the remodelling involves cellular changes that are reminiscent of dedifferentiation and are characterised by cellular volume increase, myolysis, glycogen accumulation, mitochondrial changes and chromatin redistribution. The absence of clear signs of degeneration in these models points towards cardiomyocyte adaptation or a mechanism of programmed cell survival. In patients with atrial fibrillation cardiomyocyte degeneration does occur along with dedifferentiation which might be the result of underlying cardiac pathologies or longer duration of atrial fibrillation. In this review we focus on structural remodelling during atrial fibrillation. The different aspects of histological and ultrastructural changes as well as their role in atrial dysfunction and cardiomyocyte survival are discussed. We briefly describe the underlying molecular remodelling. and possible mechanisms responsible for remodelling involving calcium overload and stretch are presented.
Thijssen
V L
VL
Department of Molecular Cell Biology, Cardiovascular Research Institute Maastricht, Maastricht University, P.O. Box 616, 6200 MD, Maastricht, The Netherlands.
Ausma
J
J
Borgers
M
M
D000818:Animals; D017209:Apoptosis; D001281:Atrial Fibrillation / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism; D016923:Cell Death; D002908:Chronic Disease; D017630:Connexins / Q000378:metabolism; D003285:Contractile Proteins / Q000378:metabolism; D005355:Fibrosis; D006041:Goats; D006325:Heart Atria; D006801:Humans; D008854:Microscopy, Electron; D023421:Models, Animal; D009206:Myocardium / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D020257:Ventricular Remodeling
D015220:Calcium Channels; D017630:Connexins; D003285:Contractile Proteins; D002118:Calcium