Reduced high shear platelet adhesion to the vascular media: defective von Willebrand factor binding to the interstitial collagen.
Fibrillar collagen serves as a thrombogenic surface for platelet adhesion mediated by von Willebrand factor (vWf) at high shear. Although abundant throughout the arterial wall, vWf-dependent platelet deposition to artery cross-sections from perfused citrated blood is localized to the adventitia of the vessel wall. Here we describe a similarly skewed distribution of vWf-binding sites in artery cross-sections. Binding of vWf-coated fluorescent beads, as well as detection of plasma vWf bound to artery cross-section at 3350 s(-1) shear rate with indirect particle-immunofluorescence or immunoelectron microscopy demonstrate vWf binding sites in the adventitia, but not in the media. A monoclonal anti-vWf antibody that interferes with vWf-binding to collagen in a microplate ELISA inhibits vWf-binding to both the adventitia and sections of collagen fibrils. Our data suggest that the media, despite its fibrillar collagen content, evidenced by electron microscopy, is defective for vWf-binding, which may explain its thromboresistant nature at high shear rates.
Komorowic
Erzsebet
E
Section of Hematology Research, Mayo Clinic and Foundation for Education and Research, Rochester, MN 55905, USA.
McBane
Robert D
RD
Charlesworth
Jon
J
Fass
David N
DN
D000818:Animals; D001665:Binding Sites; D002339:Carotid Arteries / Q000378:metabolism* / Q000648:ultrastructure; D024042:Collagen Type I / Q000378:metabolism*; D024061:Collagen Type III / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D018056:Hemorheology; D006487:Hemostasis; D006801:Humans; D007150:Immunohistochemistry; D008323:Mammary Arteries / Q000378:metabolism* / Q000648:ultrastructure; D008856:Microscopy, Fluorescence; D016253:Microscopy, Immunoelectron; D010973:Platelet Adhesiveness; D011485:Protein Binding; D012077:Renal Artery / Q000378:metabolism* / Q000648:ultrastructure; D013314:Stress, Mechanical; D013552:Swine; D014841:von Willebrand Factor / Q000378:metabolism*
D024042:Collagen Type I; D024061:Collagen Type III; D014841:von Willebrand Factor