Role of platelets in atherothrombosis.
Platelets play a pivotal role in atherothrombosis and therefore are primary targets of antithrombotic therapy. They release an array of agonists, such as adenosine diphosphate (ADP); adhesive molecules, such as P-selectin, thrombospondin, fibrinogen, and von Willebrand factor; coagulation factors; and growth factors. In turn, they present transmembrane receptors for a plethora of agonists and ligands. Heterodimeric glycoproteins of the integrin family bind extracellular matrix and plasma proteins; mediate adhesion, activation, spreading, and aggregation; and facilitate intercellular bidirectional signal transduction. Glycoprotein IIb/IIIa is the most abundant platelet integrin and membrane surface glycoprotein. Glycolipids, heparins, proteoglycans, tetraspanins, and a multitude of other molecules, such as tumor necrosis factor-alpha, CD40L, growth arrest-specific 6, Eph receptor tyrosine kinases, and signaling lymphocytic activation molecule receptors, have been implicated in atherothrombosis. ADP promotes platelet aggregation by binding to platelet surface receptors P2Y(1) and P2Y(12); the thienopyridines inhibit aggregation by binding covalently to P2Y(12). Thrombin, a potent initiator of platelet aggregation, activates platelets by cleaving protease-activated receptors (PARs) PAR-1 and PAR-4 and further propagates its effect by activating nearby platelets. A number of pharmacologic agents with antiplatelet actions have been developed, but the search continues for agents that strike an optimal balance between control of thrombosis and serious bleeding.
Jennings
Lisa K
LK
Vascular Biology Center of Excellence, Department of Internal Medicine, University of Memphis, Tennessee, USA.
D050197:Atherosclerosis / Q000188:drug therapy / Q000503:physiopathology; D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology*; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D006801:Humans; D015539:Platelet Activation / Q000187:drug effects / Q000502:physiology; D010974:Platelet Aggregation / Q000187:drug effects / Q000502:physiology; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000187:drug effects / Q000502:physiology*; D013927:Thrombosis / Q000188:drug therapy / Q000503:physiopathology
D005343:Fibrinolytic Agents; D019039:Platelet Glycoprotein GPIIb-IIIa Complex