Regulation of von Willebrand factor-platelet interactions.
The formation of thrombi is a multistep process involving several components, including von Willebrand factor (VWF). VWF is an adhesive multimeric protein, which acts as a molecular bridge between the subendothelial matrix and the glycoprotein Ib/IX/V receptor complex. Furthermore, VWF promotes the expansion of the platelet plug by cross-linking platelets via binding to integrin alphaIIbbeta3. In terms of thrombus formation, it is essential that VWF-platelet interactions occur timely, that is: it should happen not too early or too late. Given the co-existence of VWF and platelets in the circulation, this implies that there must be regulatory mechanisms that prevent premature formation of VWF-rich platelet aggregates that could occlude the vasculature. Indeed, several mechanisms have been identified at the level of VWF, which are dedicated to the prevention of excessive VWF-platelet interactions following endothelial release of VWF (which may include limited exposure to shear stress, the presence of Mg2+ ions, inhibition of VWF-platelet interactions by endothelial proteins, ADAMTS13-mediated proteolysis) and of circulating VWF-platelet aggregates during normal circulation (shielding of the platelet-binding A1 domain by other regions of the VWF molecule, inhibition of VWF-platelet interactions by beta2-glycoprotein I). In the present review an overview of these mechanisms will be discussed.
INSERM U 770, 80 rue du Général Leclerc, 94276 Le Kremlin-Bicetre, France. peter.lenting@inserm.fr
Peter J
PJ
Lenting
Julie N
JN
Pegon
Evelyn
E
Groot
Philip G
PG
de Groot
D051722:ADAM Proteins / Q000097:blood; D000818:Animals; D001792:Blood Platelets / Q000378:metabolism*; D006801:Humans; D015539:Platelet Activation; D011499:Protein Processing, Post-Translational; D013927:Thrombosis / Q000097:blood*; D053482:beta 2-Glycoprotein I / Q000097:blood; D014842:von Willebrand Diseases / Q000097:blood*; D014841:von Willebrand Factor / Q000378:metabolism*
D053482:beta 2-Glycoprotein I; D014841:von Willebrand Factor; D051722:ADAM Proteins