Collagen receptors as potential targets for novel anti-platelet agents.
Platelets have important roles in atherosclerosis and thrombosis and their inhibition reduces the risk of these disorders. There is still a need for platelet inhibitors affecting pathways that reduce thrombosis and atherosclerosis while leaving normal hemostasis relatively unaffected, thus reducing possible bleeding complications. Although combinations show progress in achieving these goals none of the present inhibitors completely fulfill these requirements. Collagen receptors offer attractive possibilities as alternative targets at early stages in platelet activation. Three major collagen receptors are assessed in this review; the alpha2beta1 integrin, responsible primarily for platelet adhesion to collagen; GPVI, the major signaling receptor for collagen; and GPIb-V-IX, which is indirectly a collagen receptor via von Willebrand factor. Several thrombosis models and experimental approaches suggest that all three are interesting targets and merit further investigation.
Clemetson
Kenneth J
KJ
Theodor Kocher Institute, University of Berne, Freiestrasse 1, CH-3012, Berne, Switzerland. clemetson@tki.unibe.ch
Clemetson
Jeannine M
JM
D000818:Animals; D050197:Atherosclerosis / Q000188:drug therapy / Q000378:metabolism; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism*; D016503:Drug Delivery Systems / Q000379:methods; D006801:Humans; D015539:Platelet Activation / Q000187:drug effects / Q000502:physiology; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage; D010980:Platelet Membrane Glycoproteins / Q000819:agonists / Q000378:metabolism; D038981:Receptors, Collagen / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D010975:Platelet Aggregation Inhibitors; D010980:Platelet Membrane Glycoproteins; D038981:Receptors, Collagen