title: Inhibition of complement component C3 reduces vein graft atherosclerosis in apolipoprotein E3-Leiden transgenic mice.
abstract: BACKGROUND
  Venous bypass grafts may fail because of development of intimal hyperplasia and accelerated atherosclerosis. Inflammation plays a major role in these processes. Complement is an important part of the immune system and participates in the regulation of inflammation. The exact role of complement in the process of accelerated atherosclerosis of vein grafts has not yet been explored, however.
  
  
  RESULTS
  To assess the role of complement in the development of vein graft atherosclerosis, a mouse model, in which a venous interposition was placed in the common carotid artery, was used. In this model, vein graft thickening appeared within 4 weeks. The expression of complement components was studied with the use of immunohistochemistry on sections of the thickened vein graft. C1q, C3, C9, and the regulatory proteins CD59 and complement receptor-related gene y could be detected in the lesions 4 weeks after surgery. Quantitative mRNA analysis for C1q, C3, CD59, and complement receptor-related gene y revealed expression of these molecules in the thickened vein graft, whereas C9 did not show local mRNA expression. Furthermore, interference with C3 activation with complement receptor-related gene y-Ig was associated with reduced vein graft thickening, reduced C3 and C9 deposition, and reduced inflammation as assessed by analysis of influx of inflammatory cells, such as leukocytes, T cells, and monocytes. In addition, changes in apoptosis and proliferation were observed. When C3 was inhibited by cobra venom factor, a similar reduction in vein graft thickening was observed.
  
  
  CONCLUSIONS
  The complement cascade is involved in vein graft thickening and may be a target for therapy in vein graft failure disease.
authors.affiliation: Gaubius Laboratory, TNO Quality of Life, Leiden, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Schepers
authors.forename: M R
authors.initials: MR
authors.lastname: de Vries
authors.forename: C J
authors.initials: CJ
authors.lastname: van Leuven
authors.forename: J M
authors.initials: JM
authors.lastname: Grimbergen
authors.forename: V M
authors.initials: VM
authors.lastname: Holers
authors.forename: M R
authors.initials: MR
authors.lastname: Daha
authors.forename: J H
authors.initials: JH
authors.lastname: van Bockel
authors.forename: P H A
authors.initials: PH
authors.lastname: Quax
mesh_terms: D000818:Animals; D053318:Apolipoprotein E3 / Q000235:genetics*; D050197:Atherosclerosis / Q000517:prevention & control*; D003176:Complement C3 / Q000037:antagonists & inhibitors*; D004036:Diet, Atherogenic; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D014185:Transplantation, Isogeneic / Q000009:adverse effects; D014684:Venae Cavae / Q000637:transplantation*
chemical_list: D053318:Apolipoprotein E3; D003176:Complement C3; C052720:apolipoprotein E3 (Leidein)