title: Contribution of endothelial injury and inflammation in early phase to vein graft failure: the causal factors impact on the development of intimal hyperplasia in murine models.
abstract: OBJECTIVE
  Autologous veins are preferred conduits in by-pass surgery. However, long-term results are hampered by limited patency due to intimal hyperplasia. Although mechanisms involved in development of intimal hyperplasia have been established, the role of inflammatory processes is still unclear. Here, we studied leukocyte recruitment and intimal hyperplasia in inferior vena cava grafts transferred to abdominal aorta in mice.
  
  
  RESULTS
  Several microscopic techniques were used to study endothelium denudation and regeneration and leukocyte recruitment on endothelium. Scanning electron microscopy demonstrated denudation of vein graft endothelium 7 days post-transfer and complete endothelial regeneration by 28 days. Examination of vein grafts transferred to mice transgenic for green fluorescent protein under Tie2 promoter in endothelial cells showed regeneration of graft endothelium from the adjacent aorta. Intravital microscopy revealed recruitment of leukocytes in vein grafts at 7 days in wild type mice, which had tapered off by 28 days. At 28 and 63 days there was significant development of intimal hyperplasia. In contrast; no injury, leukocyte recruitment nor intimal hyperplasia occurred in arterial grafts. Leukocyte recruitment was reduced in vein grafts in mice deficient in E- and P-selectin. In parallel, intimal hyperplasia was reduced in vein grafts in mice deficient in E- and P-selectin and in wild type mice receiving P-selectin/E-selectin function-blocking antibodies.
  
  
  CONCLUSIONS
  The results show that early phase endothelial injury and inflammation are crucial processes in intimal hyperplasia in murine vein grafts. The data implicate endothelial selectins as targets for intervention of vein graft disease.
authors.affiliation: Department of Molecular Medicine and Surgery, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Chi-Nan
authors.initials: CN
authors.lastname: Tseng
authors.affiliation: Department of Molecular Medicine and Surgery, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Eva
authors.initials: E
authors.lastname: Karlöf
authors.affiliation: Department of Molecular Medicine and Surgery, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Ya-Ting
authors.initials: YT
authors.lastname: Chang
authors.affiliation: Department of Molecular Medicine and Surgery, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Mariette
authors.initials: M
authors.lastname: Lengquist
authors.affiliation: Department of Molecular Medicine and Surgery, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Pierre
authors.initials: P
authors.lastname: Rotzius
authors.affiliation: The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Per-Olof
authors.initials: PO
authors.lastname: Berggren
authors.affiliation: Department of Molecular Medicine and Surgery, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Ulf
authors.initials: U
authors.lastname: Hedin
authors.affiliation: Department of Molecular Medicine and Surgery, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Einar E
authors.initials: EE
authors.lastname: Eriksson
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D019040:E-Selectin / Q000235:genetics; D004730:Endothelium, Vascular / Q000276:immunology / Q000293:injuries*; D006084:Graft Rejection / Q000209:etiology* / Q000276:immunology; D006965:Hyperplasia / Q000209:etiology / Q000276:immunology / Q000473:pathology; D007249:Inflammation / Q000276:immunology; D007962:Leukocytes / Q000276:immunology; D051379:Mice; D019007:P-Selectin / Q000235:genetics; D017539:Tunica Intima / Q000276:immunology / Q000473:pathology*; D014680:Veins / Q000276:immunology / Q000473:pathology / Q000637:transplantation*
chemical_list: D019040:E-Selectin; D019007:P-Selectin