Microparticles in atrial fibrillation: a link between cell activation or apoptosis, tissue remodelling and thrombogenicity.

Microparticles (MPs) are small membrane vesicles that are shed from virtually all cells in response to stress. Widely described in atherothrombotic diseases, recent data suggest a role for circulating MPs in the hypercoagulable state associated with supraventricular tachyarrhythmia. During atrial fibrillation, several mechanisms, such as high ventricular heart rate, low or oscillatory shear stress, stretch, hypoxia, inflammation and oxidative stress, are potent inducers of apoptotic cell death, which leads to the shedding of procoagulant MPs within the vasculature. As key regulators of cell-cell cross-talk and important mediators of inflammatory, thrombogenic and proteolytic pathways, MPs directly or indirectly contribute to the amplification loops involved in atrial fibrillation. Because high levels of platelets and endothelial-derived MPs are identified during stroke and are associated with infarct size and clinical outcome, they are proposed to be a potent marker of ischaemic risk. During pulmonary vein isolation, the additional increases of platelet and leukocyte MP levels suggest the extent of tissue damage and reflect a transient activation of the coagulation cascade that could favour ischaemic stroke. Conversely, the observed decreases of several apoptotic markers some months after the restoration of sinus rhythm suggest that the extent of apoptotic processes is reversible and might enable restoration of haemostasis. In this review, we will summarise the current evidence supporting the roles of apoptosis and cell activation in the development of the prothrombotic state observed in atrial fibrillation, with a particular focus on procoagulant MPs.