title: Osteoprotegerin is associated with aneurysm diameter and proteolysis in abdominal aortic aneurysm disease.
abstract: OBJECTIVE
  Serum osteoprotegerin (OPG) concentrations have previously been associated with growth of abdominal aortic aneurysms (AAAs). In vitro experiments showed that OPG promotes matrix metalloprotease (MMP) release from monocytes and vascular smooth muscle cells. We hypothesized that OPG expression is increased in human AAAs and is associated with proteolysis.
  
  
  RESULTS
  AAA biopsies were collected from 329 patients. We assessed the concentrations of OPG, cathepsins A, B, and S as well as the activity of MMP-2 and MMP-9. The AAA wall infiltration by macrophages, lymphocytes, and plasma cells was estimated by immunohistochemistry. The concentration of OPG correlated positively with aortic diameter (<55 mm: 16.1 [5.8-28.7], 55-70 mm: 21.9 [10.2-36.0], >70 mm: 24.0 [13.5-52.9] ng OPG/mg total amount of protein, P=0.020), cathepsin A (r=0.221, P=0.005), B (r=0.384, P<0.001), and S (r=0.467, P<0.001), MMP-2 (r=0.180, P<0.001), MMP-9 (r=0.178, P<0.001), and the number of lymphocytes (P<0.001) and plasma cells (P=0.001). OPG immunostaining was predominantly demonstrated in plasma cells.
  
  
  CONCLUSIONS
  The concentration of aortic wall OPG is positively associated with established markers of AAA severity and pathogenesis. OPG appeared to be associated with lymphocytes and plasma cells. These human data support previous experimental data suggesting a role for OPG in AAA pathogenesis.
authors.affiliation: Department of Vascular Surgery, Room G04.129, University Medical Center Utrecht, PO Box 85500, 3508 GA Utrecht, The Netherlands. D.Koole@umcutrecht.nl
authors.forename: Dave
authors.initials: D
authors.lastname: Koole
authors.forename: Rob
authors.initials: R
authors.lastname: Hurks
authors.forename: Arjan
authors.initials: A
authors.lastname: Schoneveld
authors.forename: Aryan
authors.initials: A
authors.lastname: Vink
authors.forename: Jonathan
authors.initials: J
authors.lastname: Golledge
authors.forename: Corey S
authors.initials: CS
authors.lastname: Moran
authors.forename: Dominique P
authors.initials: DP
authors.lastname: de Kleijn
authors.forename: Joost A
authors.initials: JA
authors.lastname: van Herwaarden
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: de Vries
authors.forename: Jon D
authors.initials: JD
authors.lastname: Laman
authors.forename: Ruth
authors.initials: R
authors.lastname: Huizinga
authors.forename: Gerard
authors.initials: G
authors.lastname: Pasterkamp
authors.forename: Frans L
authors.initials: FL
authors.lastname: Moll
mesh_terms: D000368:Aged; D001012:Aorta, Abdominal / Q000201:enzymology* / Q000473:pathology; D017544:Aortic Aneurysm, Abdominal / Q000201:enzymology* / Q000473:pathology; D015415:Biomarkers / Q000032:analysis; D001706:Biopsy; D002403:Cathepsins / Q000032:analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016014:Linear Models; D008214:Lymphocytes / Q000201:enzymology; D008264:Macrophages / Q000201:enzymology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000032:analysis; D020780:Matrix Metalloproteinase 9 / Q000032:analysis; D008875:Middle Aged; D009426:Netherlands; D053244:Osteoprotegerin / Q000032:analysis*; D010447:Peptide Hydrolases / Q000032:analysis*; D010950:Plasma Cells / Q000201:enzymology; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers; D053244:Osteoprotegerin; C506030:TNFRSF11B protein, human; D002403:Cathepsins; D010447:Peptide Hydrolases; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9