The presence of active von Willebrand factor under various pathological conditions

ADAMTS-13 is a crucial metalloproteinase involved in liberating fragments of von Willebrand factor (vWF) into the plasma as well as regulating its activity by cleaving "ultra-large" multimers into smaller and less active counterparts. Many pathological conditions, including those emerged during pregnancy are characterized by increased level of vWF and decreased ADAMTS-13 activity. In this regard, it is necessary to monitor the levels of vWF and ADAMTS-13 activity to prevent thrombotic thrombocytopenic purpura (Moschcowitz disease) as one of the most severe forms of thrombotic microangiopathy.

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The ADAMTS metalloproteinases

Biochemical Journal ◽

10.1042/bj20040424 ◽

2005 ◽

Vol 386 (1) ◽

pp. 15-27 ◽

Cited By ~ 476

Author(s):

Sarah PORTER ◽

Ian M. CLARK ◽

Lara KEVORKIAN ◽

Dylan R. EDWARDS

Keyword(s):

Von Willebrand Factor ◽

Structural Organization ◽

Altered Expression ◽

Functional Roles ◽

Pathological Conditions ◽

The Matrix ◽

Inhibition Of Angiogenesis ◽

Von Willebrand ◽

Willebrand Factor ◽

Human Family

The ADAMTSs (adisintegrin and metalloproteinase with thrombospondin motifs) are a group of proteases that are found both in mammals and invertebrates. Since the prototype ADAMTS-1 was first described in 1997, there has been a rapidly expanding body of literature describing this gene family and the proteins they encode. The complete human family has 19 ADAMTS genes, together with three members of a newly identified subgroup, the ADAMTSL (ADAMTS-like) proteins, which have several domains in common with the ADAMTSs. The ADAMTSs are extracellular, multidomain enzymes whose known functions include: (i) collagen processing as procollagen N-proteinase; (ii) cleavage of the matrix proteoglycans aggrecan, versican and brevican; (iii) inhibition of angiogenesis; and (iv) blood coagulation homoeostasis as the von Willebrand factor cleaving protease. Roles in organogenesis, inflammation and fertility are also apparent. Recently, some ADAMTS genes have been found to show altered expression in arthritis and various cancers. This review highlights progress in understanding the structural organization and functional roles of the ADAMTSs in normal and pathological conditions.

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Von Willebrand Factor in Health and Disease

Biochemistry (Moscow) Supplement Series A Membrane and Cell Biology ◽

10.1134/s1990747821040036 ◽

2021 ◽

Vol 15 (3) ◽

pp. 201-218

Author(s):

P. P. Avdonin ◽

N. V. Tsvetaeva ◽

N. V. Goncharov ◽

E. Yu. Rybakova ◽

S. K. Trufanov ◽

...

Keyword(s):

Molecular Weight ◽

Von Willebrand Factor ◽

Thrombus Formation ◽

The Body ◽

Pathological Conditions ◽

Activated Platelets ◽

History Of ◽

Health And Disease ◽

Von Willebrand ◽

Willebrand Factor

Abstract— Von Willebrand factor (vWF), the key component of hemostasis, is synthesized in endothelial cells and megakaryocytes and released into the blood as high molecular weight multimeric glycoproteins weighing up to 20 million Daltons. Blood plasma metalloprotease ADAMTS13 cleaves ultra-large vWF multimers to smaller multimeric and oligomeric molecules. The vWF molecules attach to the sites of damage at the surface of arterioles and capillaries and unfold under conditions of shear stress. On the unfolded vWF molecule, the regions interacting with receptors on the platelet membrane are exposed. After binding to the vWF filaments, platelets are activated; platelets circulating in the vessels are additionally attached to them, leading to thrombus formation, blocking of microvessels, and cessation of bleeding. This review describes the history of the discovery of vWF, presents data on the mechanisms of vWF secretion and its structure, and characterizes the processes of vWF metabolism in the body under normal and pathological conditions.

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