Platelet adhesion receptors: novel targets for anti-thrombotic therapy.
The critical role of platelets in the development of the acute coronary syndromes is now well recognised, and a great deal of effort has therefore focused on elucidating the key adhesion receptors mediating platelet-vessel wall and platelet-platelet interactions. The vascular adhesion protein von Willebrand factor (vWf) plays a key role in supporting platelet adhesion to the damaged vessel wall and binds to two adhesion receptors on the platelet surface, the glycoprotein (GP) Ib-V-IX complex and glycoprotein IIb-IIIa. The GP Ib-V-IX complex is a unique adhesion receptor which enables platelets to roll on a vWf matrix under conditions of rapid blood flow as well as transducing signals leading to the activation of GP IIb-IIIa. This latter receptor binds to a distinct site on vWf and is essential for stabilising platelet adhesion to the site of vessel wall injury. In addition to supporting platelet adhesion, GP IIb-IIIa plays a key role in a number of other platelet responses including platelet spreading, aggregation, the release of procoagulant-rich microvesicles, and clot retraction. Given its central role in platelet function GP IIb-IIIa has become an attractive target for the development of novel anti-thrombotic agents. In this paper, we consider the advantages of inhibitors of GP IIb-IIIa compared with other established anti-platelet drugs including aspirin and ticlopidine, and also discuss some potential problems associated with the inhibition of GP IIb/IIIa and other platelet adhesion receptors.
Williamson
D
D
Thrombogenix Pty Ltd, Australian Centre for Blood Diseases, Department of Medicine, Monash Medical School, Melbourne, Vic.
Giuliano
S
S
Jackson
S P
SP
D000077284:Abciximab; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D006487:Hemostasis / Q000502:physiology; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology; D010973:Platelet Adhesiveness / Q000187:drug effects / Q000502:physiology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors / Q000502:physiology*; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000502:physiology; D014841:von Willebrand Factor / Q000502:physiology
D000911:Antibodies, Monoclonal; D005343:Fibrinolytic Agents; D007140:Immunoglobulin Fab Fragments; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D019038:Platelet Glycoprotein GPIb-IX Complex; D014841:von Willebrand Factor; D000077284:Abciximab