title: Autoantibodies to heat shock protein 60 promote thrombus formation in a murine model of arterial thrombosis.
abstract: OBJECTIVE
  Anti-heat shock protein (HSP)60 autoantibodies are associated with atherosclerosis and are known to affect endothelial cells in vitro. However, their role in thrombus formation remains unclear. We hypothesized that anti-HSP60 autoantibodies could potentiate thrombosis, and evaluated the effect of anti-murine HSP60 antibodies in a ferric chloride (FeCl3)-induced murine model of carotid artery injury.
  
  
  METHODS
  Anti-HSP60, or control, IgG was administered to BALB/c mice 48 h prior to inducing carotid artery injury, and blood flow was monitored using an ultrasound probe.
  
  
  RESULTS
  Thrombus formation was more rapid and stable in anti-HSP60 IGG-treated mice than in controls (blood flow=1.7%+/-0.6% vs. 34%+/-12.6%, P=0.0157). Occlusion was complete in all anti-HSP60 IgG-treated mice (13/13), with no reperfusion being observed. In contrast, 64% (9/14) of control mice had complete occlusion, with reperfusion occurring in 6/9 mice. Thrombi were significantly larger in anti-HSP60 IgG-treated mice (P=0.0001), and contained four-fold more inflammatory cells (P=0.0281) than in controls. Non-injured contralateral arteries of anti-HSP60 IgG-treated mice were also affected, exhibiting abnormal endothelial cell morphology and significantly greater von Willebrand factor (VWF) and P-selectin expression than control mice (P=0.0024 and P=0.001, respectively).
  
  
  CONCLUSIONS
  In summary, the presence of circulating anti-HSP60 autoantibodies resulted in increased P-selectin and VWF expression and altered cell morphology in endothelial cells lining uninjured carotid arteries, and promoted thrombosis and inflammatory cell recruitment in FeCl3-injured carotid arteries. These findings suggest that anti-HSP60 autoantibodies may constitute an important prothrombotic risk factor in cardiovascular disease in human vascular disease.
authors.affiliation: Division of Rheumatology, The Research Institute of the McGill University Health Centre, McGill University, Montreal, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Dieudé
authors.forename: M-A
authors.initials: MA
authors.lastname: Gillis
authors.forename: J-F
authors.initials: JF
authors.lastname: Théorêt
authors.forename: E
authors.initials: E
authors.lastname: Thorin
authors.forename: G
authors.initials: G
authors.lastname: Lajoie
authors.forename: J S
authors.initials: JS
authors.lastname: Levine
authors.forename: Y
authors.initials: Y
authors.lastname: Merhi
authors.forename: J
authors.initials: J
authors.lastname: Rauch
mesh_terms: D000818:Animals; D001157:Arterial Occlusive Diseases / Q000209:etiology / Q000276:immunology; D001323:Autoantibodies / Q000008:administration & dosage / Q000494:pharmacology*; D002340:Carotid Artery Diseases / Q000209:etiology / Q000276:immunology; D018834:Chaperonin 60 / Q000276:immunology*; D002712:Chlorides; D004195:Disease Models, Animal; D005290:Ferric Compounds; D051379:Mice; D019007:P-Selectin / Q000032:analysis; D012039:Regional Blood Flow; D015424:Reperfusion; D013927:Thrombosis / Q000209:etiology / Q000276:immunology*; D014841:von Willebrand Factor / Q000032:analysis
chemical_list: D001323:Autoantibodies; D018834:Chaperonin 60; D002712:Chlorides; D005290:Ferric Compounds; D019007:P-Selectin; D014841:von Willebrand Factor; C024555:ferric chloride