title: 18F-FDG uptake assessed by PET/CT in abdominal aortic aneurysms is associated with cellular and molecular alterations prefacing wall deterioration and rupture.
abstract: Rupture of abdominal aortic aneurysms (AAAs) leads to a significant morbidity and mortality in aging populations, and its prediction would be most beneficial to public health. Spots positive for uptake of (18)F-FDG detected by PET are found in 12% of AAA patients (PET+), who are most often symptomatic and at high rupture risk. Comparing the (18)F-FDG-positive site with a negative site from the same aneurysm and with samples collected from AAA patients with no (18)F-FDG uptake should allow the discrimination of biologic alterations that would help in identifying markers predictive of rupture.
  
  
  METHODS
  Biopsies of the AAA wall were obtained from patients with no (18)F-FDG uptake (PET0, n = 10) and from PET+ patients (n = 8), both at the site positive for uptake and at a distant negative site of the aneurysmal wall. Samples were analyzed by immunohistochemistry, quantitative real-time polymerase chain reaction, and zymography.
  
  
  RESULTS
  The sites of the aneurysmal wall with a positive (18)F-FDG uptake were characterized by a strikingly increased number of adventitial inflammatory cells, highly proliferative, and by a drastic reduction of smooth muscle cells (SMCs) in the media as compared with their negative counterpart and with the PET0 wall. The expression of a series of genes involved in the maintenance and remodeling of the wall was significantly modified in the negative sites of PET+, compared with the PET0 wall, suggesting a systemic alteration of the aneurysmal wall. Furthermore, a striking increase of several matrix metalloproteinases (MMPs), notably the MMP1 and MMP13 collagenases, was observed in the positive sites, mainly in the adventitia. Moreover, PET+ patients were characterized by a higher circulating C-reactive protein.
  
  
  CONCLUSIONS
  Positive (18)F-FDG uptake in the aneurysmal wall is associated with an active inflammatory process characterized by a dense infiltrate of proliferating leukocytes in the adventitia and an increased circulating C-reactive protein. Moreover, a loss of SMC in the media and alterations of the expression of genes involved in the remodeling of adventitia and collagen degradation potentially participate in the weakening of the aneurysmal wall preceding rupture.
authors.affiliation: Laboratory of Connective Tissues Biology, GIGA-R, University of Liège, Sart-Tilman, Belgium.
authors.forename: Audrey
authors.initials: A
authors.lastname: Courtois
authors.forename: Betty V
authors.initials: BV
authors.lastname: Nusgens
authors.forename: Roland
authors.initials: R
authors.lastname: Hustinx
authors.forename: Gauthier
authors.initials: G
authors.lastname: Namur
authors.forename: Pierre
authors.initials: P
authors.lastname: Gomez
authors.forename: Joan
authors.initials: J
authors.lastname: Somja
authors.forename: Jean-Olivier
authors.initials: JO
authors.lastname: Defraigne
authors.forename: Philippe
authors.initials: P
authors.lastname: Delvenne
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Michel
authors.forename: Alain C
authors.initials: AC
authors.lastname: Colige
authors.forename: Natzi
authors.initials: N
authors.lastname: Sakalihasan
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001012:Aorta, Abdominal / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology*; D017544:Aortic Aneurysm, Abdominal / Q000000981:diagnostic imaging / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D001019:Aortic Rupture / Q000000981:diagnostic imaging / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D001692:Biological Transport; D015415:Biomarkers / Q000378:metabolism; D004789:Enzyme Activation; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism*; D020869:Gene Expression Profiling; D006801:Humans; D007962:Leukocytes / Q000276:immunology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D064847:Multimodal Imaging; D049268:Positron-Emission Tomography; D011379:Prognosis; D014057:Tomography, X-Ray Computed
chemical_list: D015415:Biomarkers; D019788:Fluorodeoxyglucose F18; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9
keywords: aneurysm; inflammation; metalloproteinases; positron emission tomography; rupture