title: C1-esterase inhibitor protects against early vein graft remodeling under arterial blood pressure.
abstract: OBJECTIVE
  Arterial pressure induced vein graft injury can result in endothelial loss, accelerated atherosclerosis and vein graft failure. Inflammation, including complement activation, is assumed to play a pivotal role herein. Here, we analyzed the effects of C1-esterase inhibitor (C1inh) on early vein graft remodeling.
  
  
  METHODS
  Human saphenous vein graft segments (n=8) were perfused in vitro with autologous blood either supplemented or not with purified human C1inh at arterial pressure for 6h. The vein segments and perfusion blood were analyzed for cell damage and complement activation. In addition, the effect of purified C1inh on vein graft remodeling was analyzed in vivo in atherosclerotic C57Bl6/ApoE3 Leiden mice, wherein donor caval veins were interpositioned in the common carotid artery.
  
  
  RESULTS
  Application of C1inh in the in vitro perfusion model resulted in significantly higher blood levels and significantly more depositions of C1inh in the vein wall. This coincided with a significant reduction in endothelial loss and deposition of C3d and C4d in the vein wall, especially in the circular layer, compared to vein segments perfused without supplemented C1inh. Administration of purified C1inh significantly inhibited vein graft intimal thickening in vivo in atherosclerotic C57Bl6/ApoE3 Leiden mice, wherein donor caval veins were interpositioned in the common carotid artery.
  
  
  CONCLUSIONS
  C1inh significantly protects against early vein graft remodeling, including loss of endothelium and intimal thickening. These data suggest that it may be worth considering its use in patients undergoing coronary artery bypass grafting.
authors.affiliation: Department of Pathology, VU University Medical Center, De Boelelaan 1117, PO Box 7057, 1007 MB Amsterdam, The Netherlands. paj.krijnen@vumc.nl
authors.forename: Paul A J
authors.initials: PA
authors.lastname: Krijnen
authors.forename: Koba
authors.initials: K
authors.lastname: Kupreishvili
authors.forename: Margreet R
authors.initials: MR
authors.lastname: de Vries
authors.forename: Abbey
authors.initials: A
authors.lastname: Schepers
authors.forename: Wim
authors.initials: W
authors.lastname: Stooker
authors.forename: Alexander B A
authors.initials: AB
authors.lastname: Vonk
authors.forename: Leon
authors.initials: L
authors.lastname: Eijsman
authors.forename: Victor W M
authors.initials: VW
authors.lastname: Van Hinsbergh
authors.forename: Sacha
authors.initials: S
authors.lastname: Zeerleder
authors.forename: Diana
authors.initials: D
authors.lastname: Wouters
authors.forename: Marieke
authors.initials: M
authors.lastname: van Ham
authors.forename: Paul H A
authors.initials: PH
authors.lastname: Quax
authors.forename: Hans W M
authors.initials: HW
authors.lastname: Niessen
mesh_terms: D000818:Animals; D053318:Apolipoprotein E3; D050197:Atherosclerosis / Q000150:complications* / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D001794:Blood Pressure; D003174:Complement C1 Inactivator Proteins / Q000494:pharmacology*; D050718:Complement C1 Inhibitor Protein; D015933:Complement C3d / Q000378:metabolism; D015935:Complement C4b / Q000378:metabolism; D001026:Coronary Artery Bypass / Q000009:adverse effects*; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000187:drug effects / Q000473:pathology; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020556:Neutrophil Infiltration; D010446:Peptide Fragments / Q000378:metabolism; D010477:Perfusion; D012501:Saphenous Vein / Q000187:drug effects* / Q000276:immunology / Q000473:pathology / Q000637:transplantation; D013997:Time Factors; D058017:Vascular Grafting / Q000009:adverse effects*; D014684:Venae Cavae / Q000187:drug effects* / Q000276:immunology / Q000473:pathology / Q000637:transplantation
chemical_list: D053318:Apolipoprotein E3; D003174:Complement C1 Inactivator Proteins; D050718:Complement C1 Inhibitor Protein; D010446:Peptide Fragments; C469952:SERPING1 protein, human; D015933:Complement C3d; D015935:Complement C4b; C032261:complement C4d