title: The potential therapeutic benefit of targeting ADAMTS13 activity.
abstract: Platelet-vessel wall interaction is mediated by von Willebrand factor (VWF), which thereby plays a major role in physiological hemostasis and thrombotic disease. VWF is released as ultralarge multimers from endothelial cells, whereupon it is cleaved by ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type I repeats-13). The prohemostatic properties of VWF are dependent of its multimeric size; hence, ADAMTS13 activity is an important determinant in platelet-vessel wall interaction. Deficiency of ADAMTS13 in its most classical form in thrombotic thrombocytopenic purpura can lead to severe thrombotic microangiopathy. However, there is a growing variety of diseases in which ADAMTS13 levels have been found to be decreased and in which reduced cleavage of VWF may play a role. Hence, targeting of VWF cleavage by pharmacological modulation of ADAMTS13 levels is an interesting approach in some of these conditions. This review discusses the available evidence for a role of ADAMTS13 in various disease states and the potential therapeutic benefit of restoration of ADAMTS13 levels.
authors: Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
authors: Elise S
authors: ES
authors: Eerenberg
authors: Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
authors: Marcel
authors: M
authors: Levi
mesh_terms: D051722:ADAM Proteins / Q000097:blood*; D000071120:ADAMTS13 Protein; D000818:Animals; D006487:Hemostasis; D006801:Humans; D011697:Purpura, Thrombotic Thrombocytopenic / Q000201:enzymology / Q000628:therapy; D013927:Thrombosis / Q000201:enzymology / Q000628:therapy; D014841:von Willebrand Factor / Q000378:metabolism*
chemical_list: D014841:von Willebrand Factor; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human