title: Platelet adhesion involves a novel interaction between vimentin and von Willebrand factor under high shear stress.
abstract: The interaction between platelet receptor glycoprotein Ibα and the A1 domain of von Willebrand factor (VWF) mediates tethering/translocation of platelets to sites of vascular injury. Unexpectedly, we observed platelets translocating over A1A2A3 domains protein slower than on A1 domain at high shear stress. This observation suggests an additional interaction between A domains and an adhesive receptor. We investigated vimentin because we have data showing the interaction of vimentin with the A2 domain of VWF. Moreover, vimentin is expressed on the platelet surface. This novel interaction was analyzed by using purified VWF, recombinant proteins, anti-vimentin antibodies, parallel flow chamber adhesion assays, flow cytometry, and vimentin-deficient murine platelets. The active form of VWF bound to vimentin, and the purified A2 domain blocked that binding. The interaction of a gain-of-function A1A2A3 mutant with platelet was reduced using anti-vimentin antibody. Platelet adhesion to wild-type (WT) A1A2A3 protein, collagen, and fibrin(ogen) was inhibited (32-75%) by anti-vimentin antibody under high shear stress. Compared with WT mice, platelets from vimentin-deficient mice had a reduced flow-dependent adhesion to both collagen and purified murine VWF. Last, the vimentin knockout mice had a prolonged tail bleeding time. The results describe that platelet vimentin engages VWF during platelet adhesion under high shear stress.
authors.affiliation: Section of Cardiovascular Research, Department of Medicine, Baylor College of Medicine, Houston, TX; and.
authors.forename: Qi
authors.initials: Q
authors.lastname: Da
authors.forename: Molly
authors.initials: M
authors.lastname: Behymer
authors.forename: Juliana I
authors.initials: JI
authors.lastname: Correa
authors.forename: K Vinod
authors.initials: KV
authors.lastname: Vijayan
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Cruz
mesh_terms: D000818:Animals; D001760:Bleeding Time; D001792:Blood Platelets / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D051379:Mice; D010973:Platelet Adhesiveness; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000378:metabolism; D011485:Protein Binding; D033081:Shear Strength; D013314:Stress, Mechanical; D014746:Vimentin / Q000378:metabolism*; D014841:von Willebrand Factor / Q000378:metabolism*
chemical_list: D007074:Immunoglobulin G; D019038:Platelet Glycoprotein GPIb-IX Complex; D014746:Vimentin; D014841:von Willebrand Factor