New aspects of pathogenesis of atrial fibrillation: remodelling of intercalated discs.

This review deals with the understanding of the role of key factors of ageing, oxidative stress and inflammation, in relation to development of age-related cardiovascular disease, atrial fibrillation. Increased production of reactive oxygen species and systemic inflammation promote cardiac structural and electrophysiologic remodeling that is crucial with respect to development and sustaining of atrial fibrillation. Data suggest that alterations in atrial connexin-43 and/or connexin-40 expression, phosphorylation and distribution affect cell-to-cell electrical coupling and molecular signalling that is proarrhythmogenic. However, studies showing causal relationship in the context of pathogenesis of atrial fibrillation are still scarce. Nevertheless, gap junctional connexin channels are considered as targets for arrhythmia prevention and therapeutic interventions aimed at mitochondria-related reactive oxygen species appear to be challenging. In addition, ageing is accompanied by abnormalities in adhesive junctions that most likely promote asynchronous contraction and arrhythmias. It is consistent with recent data that highlight a new perspective in regulation of intercalated disc function via adhesive junctions, fascia adherens and desmosomes. The crosstalk between adhesive and gap junctions is suggested to be implicated in pathogenesis of arrhythmias. On the other hand, modulation of adhesive proteins, N-cadherin and catenin may be promising tool aimed to synchronize heart function. Despite the progress in this field many questions remain to be answered by further research.