title: C-reactive protein induces expression of tissue factor and plasminogen activator inhibitor-1 and promotes fibrin accumulation in vein grafts.
abstract: BACKGROUND
  C-reactive protein (CRP) promotes tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1) expression in vitro, and an elevated plasma CRP concentration is associated with an increased risk of vein graft (VG) thrombosis after coronary artery bypass surgery. However, little is known about the effects of CRP on VG TF and PAI-1 expression in vivo, or on VG thrombosis.
  
  
  OBJECTIVE
  We studied transgenic (Tg) mice expressing human CRP in a VG model to explore in vivo cause-and-effect relationships between CRP and TF, PAI-1, and VG thrombosis.
  
  
  METHODS
  Vein segments from wild-type (WT) and CRP-Tg donors were transplanted into carotid arteries of WT and CRP-Tg recipients. VGs were analyzed 1-4 weeks later.
  
  
  RESULTS
  Human CRP accumulated in VGs during the first 4 weeks after surgery, but appeared to originate exclusively from systemic sources, rather than local production. Human CRP significantly increased TF gene expression, protein concentration and activity in VGs. Human CRP also increased PAI-1 concentrations in VGs, although only in vascular endothelial cells. Human CRP stimulated macrophage migration, invasion into VGs, and TF expression. Fibrin deposition was significantly greater in VGs of CRP-Tg mice than in WT controls.
  
  
  CONCLUSIONS
  CRP accumulates in VGs early after surgery, originating from systemic sources rather than local synthesis. Human CRP promotes TF and PAI-1 expression in VGs, although with different expression patterns. Human CRP stimulates macrophage invasion and fibrin deposition within VGs. These results suggest that CRP induces pathologic changes in VGs that contribute to early VG occlusion.
authors: Department of Medicine and Medical Pharmacology and Physiology, School of Medicine, University of Missouri, Columbia, MO, USA.
authors: Y
authors: Y
authors: Ji
authors: P M
authors: PM
authors: Fish
authors: T L
authors: TL
authors: Strawn
authors: A W
authors: AW
authors: Lohman
authors: J
authors: J
authors: Wu
authors: A J
authors: AJ
authors: Szalai
authors: W P
authors: WP
authors: Fay
mesh_terms: D000818:Animals; D002097:C-Reactive Protein / Q000378:metabolism*; D002465:Cell Movement; D002712:Chlorides / Q000737:chemistry; D001026:Coronary Artery Bypass; D005290:Ferric Compounds / Q000737:chemistry; D005337:Fibrin / Q000378:metabolism*; D006801:Humans; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D013925:Thromboplastin / Q000378:metabolism*; D019076:Transgenes; D014680:Veins / Q000637:transplantation*; D020246:Venous Thrombosis / Q000097:blood
chemical_list: D002712:Chlorides; D005290:Ferric Compounds; D017395:Plasminogen Activator Inhibitor 1; D011994:Recombinant Proteins; C051321:SERPINE1 protein, human; D005337:Fibrin; D002097:C-Reactive Protein; D013925:Thromboplastin; C024555:ferric chloride
keywords: C-reactive protein; plasminogen activator inhibitor 1; thrombosis; tissue factor; vascular graft occlusion