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Title: Von Willebrand factor and ADAMTS13 in stroke, thrombotic thrombocytopenic purpura, and malaria
Other Titles: Von Willebrand factor en ADAMTS13 in beroerte, trombotische trombocytopenische purpura, en malaria ,,
Authors: Verhenne, Sebastien
Issue Date: 16-Dec-2016
Abstract: Von Willebrand factor (VWF) is a multimeric glycoprotein that plays an important role in hemostasis. It is synthesized in endothelial cells and megakaryocytes, and circulates in plasma and platelets. VWF recruits platelets to sites of vascular injury which results in the formation of a primary platelet plug sealing off the injured blood vessel wall. The platelet-binding capacity of VWF depends on its length, with the large ones being the most reactive. Under certain conditions, hyperactive ‘ultra large’ (UL-)VWF multimers are released from intracellular storage granules into the circulation. Persistence of these hyperactive multimeric forms can cause spontaneous platelet aggregation that lead to the deposition of VWF-rich thrombi and obstruction of blood flow in microvascular beds of various organs, which is observed in the life-threatening disorder known as thrombotic thrombocytopenic purpura (TTP). In normal circulation, however, these hyperactive UL-VWF multimers are cleaved into smaller, less active fragments by the VWF-cleaving protease, called ADAMTS13. The general aim of this PhD thesis was to study different aspects of VWF and ADAMTS13 in stroke, thrombotic thrombocytopenic purpura, and malaria. More specifically, we wanted (I) to gain more insight in the relative importance of plasma VWF and platelet-derived VWF in hemostatic and thrombotic processes, (II) to develop a non-viral gene therapy for congenital TTP, and (III) to unravel the potential involvement of the VWF/ADAMTS13 axis in malaria pathophysiology using a murine model of malaria-associated lung pathology.
Publication status: published
KU Leuven publication type: TH
Appears in Collections:Molecular Virology and Gene Therapy
Chemistry - miscellaneous
Chemistry, Campus Kulak Kortrijk
Department of Cardiovascular Sciences - miscellaneous
Cardiovascular Sciences, Campus Kulak Kortrijk

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