title: Enhanced platelet adhesion and aggregation by endothelial cell-derived unusually large multimers of von Willebrand factor.
abstract: Endothelial cells synthesize and secrete von Willebrand factor (VWF) multimers, including unusually large forms (ULVWF), which are usually cleaved into smaller multimers found in normal plasma (P-VWF). Thrombotic thrombocytopenic purpura (TTP) is a microangiopathic disorder characterized by systemic attachment of platelets to inadequately cleaved ULVWF multimers. We have compared ULVWF and P-VWF in their capacity to become immobilized onto surfaces in vitro and their ability to mediate platelet adhesion. We have also used functional assays to directly compare ULVWF forms with purified P-VWF in mediating platelet aggregation in solution. At comparable concentrations, ULVWF is more effectively adsorbed onto glass surfaces than P-VWF and supports increased platelet adhesion. ULVWF is also significantly more potent than P-VWF in mediating both shear-induced platelet aggregation and ristocetin-mediated platelet agglutination.
authors.affiliation: Department of Bioengineering, Rice University, Houston, TX, USA.
authors.forename: R Anand
authors.initials: RA
authors.lastname: Kumar
authors.forename: Joel L
authors.initials: JL
authors.lastname: Moake
authors.forename: Leticia
authors.initials: L
authors.lastname: Nolasco
authors.forename: Angela L
authors.initials: AL
authors.lastname: Bergeron
authors.forename: Carol
authors.initials: C
authors.lastname: Sun
authors.forename: Jing-fei
authors.initials: JF
authors.lastname: Dong
authors.forename: Larry V
authors.initials: LV
authors.lastname: McIntire
mesh_terms: D000328:Adult; D042783:Endothelial Cells / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology* / Q000502:physiology; D006801:Humans; D008970:Molecular Weight; D010973:Platelet Adhesiveness / Q000187:drug effects / Q000502:physiology*; D010974:Platelet Aggregation / Q000187:drug effects / Q000502:physiology*; D011697:Purpura, Thrombotic Thrombocytopenic / Q000097:blood; D012310:Ristocetin / Q000494:pharmacology; D013314:Stress, Mechanical; D014841:von Willebrand Factor / Q000737:chemistry / Q000502:physiology*
chemical_list: D014841:von Willebrand Factor; D012310:Ristocetin