Purinergic receptors and atherosclerosis: Emerging role for vessel wall P2Y12

摘要

Platelets play a key role in primary haemostasis and also represent an important interface between thrombosis, immunity, and atherogenesis. Platelet-triggered inflammatory pathways contribute to the formation of atherosclerotic lesions and atherothrombosis. Platelets express receptors for a variety of agonists that initiate platelet activation, which is then amplified and sustained by activation of the G-protein-coupled puriner-gic receptor P2Y_(12). P2Y_(12) mediates platelet aggregation and secretion of platelet granule contents in response to ADP. P2Y_(12) is also a well-established target for anti-thrombotic drugs, such as the thienopyridine compounds ticlopidine, clopidogrel, and prasugrel or the direct, reversible antagonists ticagrelor, cangrelor, and elinogrel. Clinical studies have shown that in addition to preventing arterial thrombus formation in patients with coronary artery syndromes or after stent implantation, anti-thrombotic/anti-platelet therapy is also associated with systemic anti-inflammatory effects. While these findings imply an important role for P2Y_(12) in the regulation of platelet functions, P2Y_(12) expression is not restricted to platelets. Indeed, accumulating data indicate that P2Y_(12) may directly mediate pro-inflammatory and atherogenic actions in the vessel wall apparently independently of platelet activation. West et al. provide evidence supporting this notion by describing a role for vessel wall, but not platelet, P2Y_(12) in the development of early atherosclerotic lesions.