Control of von Willebrand factor multimer size and implications for disease.
Plasma von Willebrand factor (vWF) is a multimeric protein that mediates adhesion of platelets to sites of vascular injury, however only the very large vWF multimers are haemostatically competent. Plasma vWF derives predominantly from the vascular endothelium and is of a smaller average multimer size to that found in the sub-endothelial matrix. The existence of plasma factors that control the size of vWF multimers and account for this difference has long been suspected. vWF cleaving protease (vWFCP), a metalloproteinase that regulates vWF multimer size by proteolytic cleavage, and thrombospondin-1 (TSP-1), a trimeric glycoprotein that uncouples multimers by reducing the disulfide-bonds which link individual subunits, are two such factors that have recently been identified. The large and ultra large vWF multimers play a central role in arterial thrombosis and agents that regulate their size hold promise as novel anti-thrombotic drugs.
Pimanda
John
J
Centre for Thrombosis and Vascular Research, School of Medical Sciences, University of New South Wales and Department of Haematology, Prince of Wales Hospital, Sydney, Australia.
Hogg
Philip
P
D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; D019281:Dimerization; D006801:Humans; D008666:Metalloendopeptidases / Q000378:metabolism / Q000502:physiology; D013927:Thrombosis / Q000209:etiology / Q000517:prevention & control; D019700:Thrombospondin 1 / Q000378:metabolism / Q000502:physiology; D014841:von Willebrand Factor / Q000378:metabolism* / Q000502:physiology
D019700:Thrombospondin 1; D014841:von Willebrand Factor; D051722:ADAM Proteins; D008666:Metalloendopeptidases; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human