title: Morphological relationships of von Willebrand factor, type VI collagen, and fibrillin in human vascular subendothelium.
abstract: von Willebrand factor (vWF) plays an important role in the process of platelet adhesion after endothelial injury by serving as a bridge between constituents of the vascular subendothelium and platelet membrane receptors. We previously presented evidence that type VI collagen microfibrils serve as a binding site for vWF in human vascular subendothelium. However, others have proposed that vWF is not associated with type VI collagen but rather with the thicker elastin-associated microfibrils, which contain several proteins including fibrillin. We therefore investigated the relationships among vWF, type VI collagen, and fibrillin in human vascular subendothelium by immunoelectron microscopy using single- and double-labeling immunogold localization techniques. In addition, we observed the three-dimensional ultrastructure of vWF-microfibril complexes by stereo paired micrographs and stereo viewer. We found that vWF co-localizes only with the type VI collagen microfibrils in subendothelium but not with fibrillin microfibrils or striated collagen. The vWF is present in subendothelium in the form of electron-dense aggregates having diameters varying between 65 and 80 nm that are closely associated with, and enmesh, the type VI collagen microfibrils and have structural similarities to intracellular Weibel-Palade bodies. The occasional co-localization of type VI collagen and fibrillin adjacent to internal elastic lamina was observed. These results are consistent with the hypothesis that type VI collagen, but not fibrillin-containing microfibrils, serves as a physiologically relevant binding site for vWF in the vascular subendothelium, where the type VI collagen-vWF complex may play an important role modulating the hemostatic response to vascular injury.
authors.affiliation: Department of Medicine, The Mount Sinai School of Medicine, New York, New York, USA.
authors.forename: X X
authors.initials: XX
authors.lastname: Wu
authors.forename: R E
authors.initials: RE
authors.lastname: Gordon
authors.forename: R W
authors.initials: RW
authors.lastname: Glanville
authors.forename: H J
authors.initials: HJ
authors.lastname: Kuo
authors.forename: R R
authors.initials: RR
authors.lastname: Uson
authors.forename: J H
authors.initials: JH
authors.lastname: Rand
mesh_terms: D003094:Collagen / Q000378:metabolism / Q000648:ultrastructure*; D004730:Endothelium, Vascular / Q000378:metabolism / Q000648:ultrastructure*; D016326:Extracellular Matrix Proteins / Q000378:metabolism / Q000648:ultrastructure*; D000071837:Fibrillins; D006801:Humans; D007150:Immunohistochemistry; D007231:Infant, Newborn; D008840:Microfilament Proteins / Q000378:metabolism / Q000648:ultrastructure*; D016253:Microscopy, Immunoelectron; D014469:Umbilical Arteries / Q000737:chemistry / Q000648:ultrastructure; D014471:Umbilical Veins / Q000737:chemistry / Q000648:ultrastructure; D014841:von Willebrand Factor / Q000378:metabolism / Q000648:ultrastructure*
chemical_list: D016326:Extracellular Matrix Proteins; D000071837:Fibrillins; D008840:Microfilament Proteins; D014841:von Willebrand Factor; D003094:Collagen