title: Arterial shear stress reduces eph-b4 expression in adult human veins.
abstract: Vein graft adaptation to the arterial environment is characterized by loss of venous identity, with reduced Ephrin type-B receptor 4 (Eph-B4) expression but without increased Ephrin-B2 expression. We examined changes of vessel identity of human saphenous veins in a flow circuit in which shear stress could be precisely controlled. Medium circulated at arterial or venous magnitudes of laminar shear stress for 24 hours; histologic, protein, and RNA analyses of vein segments were performed. Vein endothelium remained viable and functional, with platelet endothelial cell adhesion molecule (PECAM)-expressing cells on the luminal surface. Venous Eph-B4 expression diminished (p = .002), Ephrin-B2 expression was not induced (p = .268), and expression of osteopontin (p = .002) was increased with exposure to arterial magnitudes of shear stress. Similar changes were not found in veins placed under venous flow or static conditions. These data show that human saphenous veins remain viable during ex vivo application of shear stress in a bioreactor, without loss of the venous endothelium. Arterial magnitudes of shear stress cause loss of venous identity without gain of arterial identity in human veins perfused ex vivo. Shear stress alone, without immunologic or hormonal influence, is capable of inducing changes in vessel identity and, specifically, loss of venous identity.
authors.affiliation: Department of Surgery, Yale School of Medicine, New Haven, Connecticut ; Vascular Biology and Therapeutics Program, Yale School of Medicine, New Haven, Connecticut.
authors.forename: Lynn S
authors.initials: LS
authors.lastname: Model
authors.affiliation: Department of Surgery, Yale School of Medicine, New Haven, Connecticut ; Vascular Biology and Therapeutics Program, Yale School of Medicine, New Haven, Connecticut.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Hall
authors.affiliation: Department of Surgery, Yale School of Medicine, New Haven, Connecticut ; Vascular Biology and Therapeutics Program, Yale School of Medicine, New Haven, Connecticut.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Wong
authors.affiliation: Department of Surgery, Yale School of Medicine, New Haven, Connecticut ; Vascular Biology and Therapeutics Program, Yale School of Medicine, New Haven, Connecticut.
authors.forename: Akihito
authors.initials: A
authors.lastname: Muto
authors.affiliation: Department of Surgery, Yale School of Medicine, New Haven, Connecticut ; Vascular Biology and Therapeutics Program, Yale School of Medicine, New Haven, Connecticut.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Kondo
authors.affiliation: Department of Surgery, Yale School of Medicine, New Haven, Connecticut ; Vascular Biology and Therapeutics Program, Yale School of Medicine, New Haven, Connecticut.
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Ziegler
authors.affiliation: Department of Surgery, Yale School of Medicine, New Haven, Connecticut ; Vascular Biology and Therapeutics Program, Yale School of Medicine, New Haven, Connecticut.
authors.forename: Amanda
authors.initials: A
authors.lastname: Feigel
authors.affiliation: Vascular Biology and Therapeutics Program, Yale School of Medicine, New Haven, Connecticut ; Department of Biomedical Engineering, Yale School of Engineering & Applied Science, New Haven, Connecticut.
authors.forename: Clay
authors.initials: C
authors.lastname: Quint
authors.affiliation: Vascular Biology and Therapeutics Program, Yale School of Medicine, New Haven, Connecticut ; Department of Biomedical Engineering, Yale School of Engineering & Applied Science, New Haven, Connecticut.
authors.forename: Laura
authors.initials: L
authors.lastname: Niklason
authors.affiliation: Department of Surgery, Yale School of Medicine, New Haven, Connecticut ; Vascular Biology and Therapeutics Program, Yale School of Medicine, New Haven, Connecticut ; VA Connecticut Healthcare System, West Haven, Connecticut.
authors.forename: Alan
authors.initials: A
authors.lastname: Dardik
mesh_terms: D000328:Adult; D017209:Apoptosis; D001158:Arteries / Q000502:physiology*; D019149:Bioreactors; D042783:Endothelial Cells / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D018056:Hemorheology; D006801:Humans; D008954:Models, Biological; D011312:Pressure; D036224:Receptor, EphB4 / Q000378:metabolism*; D012501:Saphenous Vein / Q000378:metabolism*; D033081:Shear Strength; D013314:Stress, Mechanical; D014022:Tissue Survival
chemical_list: D036224:Receptor, EphB4
keywords: EphB4; Ephrin-B2; Saphenous vein; bioreactor; osteopontin; shear stress; vein graft adaptation