Percutaneous transluminal coronary angioplasty (PTCA) with or without vascular stenting is commonly used to treat coronary heart disease. However, restenosis occurs in 30-50% of patients undergoing simple balloon angioplasty and in 10-30% of patients who receive an intravascular stent. Collagen exposure at the vascular damage site leads to platelet adhesion and aggregation mainly via the activation of glycoprotein (GP) VI (a primary platelet collagen receptor), which contributes to the generation of thromboxane (TX) A2 . It is produced from arachidonic acid by the activity of cyclooxygenase (COX)-1. TXA2 is a potent mediator of platelet aggregation, vasoconstriction, and vascular smooth muscle cells (VSMC) proliferation and migration. In patients undergoing PTCA, an early increase of the systemic biosynthesis of TXA2 occurs and is largely suppressed by low-dose Aspirin, a selective inhibitor of platelet COX-1. Thus, platelet activation and enhanced TXA2 biosynthesis in response to vascular damage and collagen exposure is an early event which may contribute to restenosis. In this review, we report and discuss the evidence obtained in vivo and in vitro that the blockage of the interaction of platelet GPVI with injured vascular components, using novel antiplatelet agents such as Revacept, represents a safe strategy to mitigate vascular restenosis. Revacept, a dimeric fusion protein of the extracellular domain of GPVI and the human Fc-fragment, inhibits collagen-mediated platelet adhesion and subsequent aggregation at the site of vascular injury. Finally, the possible utility of this pharmacological approach in the prevention of tumor metastasis is discussed.
Revacept, GPVI, PTCA, Restenosis, Platelets, Collagen, TXA2, Aspirin, Tumor Metastasis