Key result
Compounds targeting platelet adhesion steps, including the VWF-GPIb and collagen axes, are reviewed for their in vivo effects and potential advantages over current antiplatelet agents.
This review highlights the potential of targeting the initial steps of platelet adhesion (e.g., VWF-GPIb and collagen interactions) as a novel strategy for developing antithrombotic drugs with possible advantages over current agents.
May support adhesion-targeted antiplatelet strategies; leaves open clinical translation pending randomized trials.
Platelet adhesion to a damaged blood vessel is the initial trigger for arterial hemostasis and thrombosis. Platelets adhere to the subendothelium through an interaction with von Willebrand factor (VWF), which forms a bridge between collagen within the damaged vessel wall and the platelet receptor glycoprotein Ib/V/IX (GPIb), an interaction especially important under high shear conditions[1]. This reversible adhesion allows platelets to roll over the damaged area, which is then followed by a firm adhesion mediated by the collagen receptors (alpha(2)beta(1), GPVI, ) in addition[2] resulting in platelet activation. This leads to the conformational activation of the platelet alpha(IIb)beta3 receptor, fibrinogen binding and finally to platelet aggregation. Over the past decades, modulation of platelet function has been a strategy for the control of cardiovascular disease. Lately, drugs have been developed that target the fibrinogen receptor alphaIIbbeta3 or the ADP receptor and many of these promising compounds have been tested in clinical trials. However the development of products that interfere with the first step of hemostasis, i.e. the platelet adhesion, has lagged behind. In this review we want to discuss (i) the in vivo studies that were performed with compounds that target proteins involved in different adhesion steps i.e. the VWF-GPIb-axis, the collagen-VWF axis and the collagen-collagen receptor axis and (ii) the possible advantages these putative new drugs could have over the current antiplatelet agents.
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Vanhoorelbeke et al. (2003) conducted a review in Cardiovascular disease. Compounds targeting platelet adhesion vs. Current antiplatelet agents was evaluated. Compounds targeting platelet adhesion steps, including the VWF-GPIb and collagen axes, are reviewed for their in vivo effects and potential advantages over current antiplatelet agents.
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