title: Degeneration and atherosclerosis inducing increased deposition of type IIA secretory phospholipase A2, C-reactive protein and complement in aortic valves cause neutrophilic granulocyte influx.
abstract: OBJECTIVE
  Recent studies have indicated that atherosclerosis-like changes are involved in the pathogenesis of aortic valve stenosis. Increased blood and valve tissue levels of C-reactive protein (CRP) have been reported in patients with aortic valve disease, although the different pathological conditions involved were not analyzed. The study aim was to monitor the deposition of CRP, its activator sPLA2-IIA and its effector complement, and the subsequent influx of neutrophilic granulocytes in degenerative and atherosclerotic aortic valves.
  
  
  METHODS
  Human tricuspid aortic valves (n = 57) obtained at autopsy included five control valves, 36 aortic valves with atherosclerotic changes, and 16 with degenerative changes. All valves were analyzed immunohistochemically for the presence of sPLA2-IIA, CRP, C3d and MPO (to detect neutrophilic granulocytes), and subsequently quantified using computer-assisted morphometry.
  
  
  RESULTS
  In aortic valves with degeneration, the areas of sPLA2-IIA, CRP and complement deposition were all significantly increased compared to control valves. These mediators were even more extensively deposited in atherosclerotically changed aortic valves. The increased deposition of these mediators coincided with a significant increase of neutrophilic granulocytes in atherosclerotic and degenerated aortic valves, compared to control valves.
  
  
  CONCLUSIONS
  The study results indicate that sPLA2-IIA, CRP, and C3d are significantly more activated in atherosclerotic aortic valves compared to degeneratively changed aortic valves. A significant increase was also identified in neutrophilic granulocytes in non-infectious, diseased valves (atherosclerosis and degeneration).
authors.affiliation: Department of Pathology, VU Medical Center, Amsterdam, The Netherlands. k.kupreishvili@vumc.nl
authors.forename: Koba
authors.initials: K
authors.lastname: Kupreishvili
authors.forename: Alexi
authors.initials: A
authors.lastname: Baidoshvili
authors.forename: Mimi
authors.initials: M
authors.lastname: ter Weeme
authors.forename: Marinus A J M
authors.initials: MA
authors.lastname: Huybregts
authors.forename: Paul A J
authors.initials: PA
authors.lastname: Krijnen
authors.forename: Victor W M
authors.initials: VW
authors.lastname: Van Hinsbergh
authors.forename: Wim
authors.initials: W
authors.lastname: Stooker
authors.forename: Leon
authors.initials: L
authors.lastname: Eijsman
authors.forename: Hans W M
authors.initials: HW
authors.lastname: Niessen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001021:Aortic Valve / Q000276:immunology* / Q000473:pathology; D001024:Aortic Valve Stenosis / Q000276:immunology* / Q000473:pathology; D050197:Atherosclerosis / Q000276:immunology* / Q000473:pathology; D001344:Autopsy; D002097:C-Reactive Protein / Q000032:analysis*; D015933:Complement C3d / Q000032:analysis*; D005260:Female; D054501:Group II Phospholipases A2 / Q000032:analysis*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D020556:Neutrophil Infiltration
chemical_list: D018836:Inflammation Mediators; D015933:Complement C3d; D002097:C-Reactive Protein; D054501:Group II Phospholipases A2