Inhibition of platelet glycoprotein Ib and its antithrombotic potential.
The platelet receptor glycoprotein (GP)Ib-IX-V complex plays a dominant role in the first steps of platelet adhesion and arterial thrombus formation. Through its interaction with the multimeric plasma protein von Willebrand factor (VWF), which is bound to the damaged subendothelial structures, GPIb-IX-V tethers the platelets from the flowing blood thereby slowing them down. This step is a prerequisite for the collagen receptors to participate in firm adhesion resulting in the formation of a first platelet layer which is the basis for further thrombus formation. Recently, other ligands for GPIb-IX-V besides the extensively studied VWF have been identified, such as: alpha-thrombin, coagulation factor XII (FXII), high molecular weight kininogen (HMWK), factor XI (FXI), integrin Mac-1 and P-selectin. In this review, the interaction of GPIb-IX-V with its different ligands is described and the anticipated or demonstrated in vivo effects are discussed.
Vanhoorelbeke
Karen
K
Laboratory for Thrombosis Research, IRC, KU Leuven Campus Kortrijk, Kortrijk, Belgium.
Ulrichts
Hans
H
Van de Walle
Gerlinde
G
Fontayne
Alexandre
A
Deckmyn
Hans
H
D000818:Animals; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D005343:Fibrinolytic Agents / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D013927:Thrombosis / Q000097:blood / Q000188:drug therapy / Q000517:prevention & control*
D005343:Fibrinolytic Agents; D019038:Platelet Glycoprotein GPIb-IX Complex; D010980:Platelet Membrane Glycoproteins