Inhibition of platelet adhesion to collagen as a new target for antithrombotic drugs.
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.
Vanhoorelbeke
K
K
Laboratory for Thrombosis Research, IRC, KU Leuven Campus Kortrijk, Belgium. Karen.Vanhoorelbeke@kulak.ac.be
Ulrichts
H
H
Schoolmeester
A
A
Deckmyn
H
H
D000818:Animals; D003094:Collagen / Q000502:physiology*; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D006801:Humans; D038982:Integrin alpha2beta1 / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D010973:Platelet Adhesiveness / Q000187:drug effects*; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D010980:Platelet Membrane Glycoproteins / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D014841:von Willebrand Factor / Q000187:drug effects / Q000378:metabolism / Q000502:physiology
D005343:Fibrinolytic Agents; D038982:Integrin alpha2beta1; D019038:Platelet Glycoprotein GPIb-IX Complex; D010980:Platelet Membrane Glycoproteins; C098341:platelet membrane glycoprotein VI; D014841:von Willebrand Factor; D003094:Collagen