Potentiation and priming of platelet activation: a potential target for antiplatelet therapy.
Ischemic cardiovascular events represent the leading cause of mortality and morbidity worldwide, and platelet aggregation and thrombus formation are the main effectors of acute arterial ischemic events. Although antiplatelet therapy is the cornerstone of antithrombotic treatment of ischemic cardiovascular disorders, available antiplatelet agents have less than satisfactory efficacy; thus, the identification of novel potential target candidates for antiplatelet therapy is highly warranted. Recent evidence suggests that several molecules that amplify the aggregation response of platelets to activating stimuli, which are either released by platelets (potentiating molecules) or present in the milieu before platelets get activated (primers), play a major role in pathologic thrombus formation without being significantly involved in primary haemostasis. These molecules appear to be a particularly appealing novel potential pharmacologic target for antiplatelet therapy. Here, we review the present knowledge on some molecules acting as potentiators or primers of platelet activation and discuss their possible pharmacologic modulation for antithrombotic purposes.
Gresele
Paolo
P
Division of Internal and Cardiovascular Medicine, Department of Internal Medicine, University of Perugia, Via Enrico dal Pozzo, Perugia, Italy. grespa@unipg.it
Falcinelli
Emanuela
E
Momi
Stefania
S
D000818:Animals; D023201:CD40 Ligand / Q000037:antagonists & inhibitors / Q000502:physiology; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000502:physiology; D006801:Humans; D020738:Leptin / Q000037:antagonists & inhibitors / Q000502:physiology; D020778:Matrix Metalloproteinase 2 / Q000502:physiology; D061965:Matrix Metalloproteinase Inhibitors; D015539:Platelet Activation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000502:physiology
D020738:Leptin; D061965:Matrix Metalloproteinase Inhibitors; D010975:Platelet Aggregation Inhibitors; D042461:Vascular Endothelial Growth Factor A; D023201:CD40 Ligand; D020778:Matrix Metalloproteinase 2; D015232:Dinoprostone