Formation and Relevance of Platelet Subpopulations

Abstract

α α-granules are the most abundant of the secretory granules, with 50-80 α-granules per platelet. The contents of the α-granules are produced by the megakaryocyte or taken up by the megakaryocyte or platelet through endocytosis. Endocytosed proteins found in the α-granule include fibrinogen and coagulation factor (F) V. αgranules contain both membrane proteins, where αIIbβ3 and P-selectin (CD62P) Platelets have two major ADP receptors, P2Y1 and P2Y12, where P2Y12 is the more abundant. The role of P2Y1 and P2Y12 is, similar to the TP receptor, to reinforce platelet activation induced by other agonists having caused dense granule release. P2Y1 and P2Y12 are both GPCRs. P2Y1 couples to Gq and mediates platelet shape change and reversible aggregation. P2Y12 couples to Gi, resulting in intracellular Ca 2+ mobilization via inhibition of adenylate cyclase. P2Y12 is the target for several common anti-platelet drugs, such as clopidogrel and ticagrelor [28]. Upon vessel damage, the extracellular matrix (ECM) becomes exposed. This contains platelet activating substances such as collagen, vWF, fibronectin, laminin and thrombospondin. If the shear rate of the damaged vessel is high, as in arteries, platelet adhesion is mediated through binding of vWF to GPIb-IX-V, whereas this interaction is not essential at lower shear rates, as in veins. Platelets in circulation bind to vWF, immobilized at the site of vessel damage. The GPIb-IX-V receptor complex has a fast on-and off-rate, allowing the platelet to roll along the vWF multimers. This slows down the platelets enough to allow adhesion, via αIIbβ3, and α2β1 [17-19], figure 1A.