title: Gene expression study in positron emission tomography-positive abdominal aortic aneurysms identifies CCL18 as a potential biomarker for rupture risk.
abstract: Rupture of abdominal aortic aneurysm (AAA) is a cause of significant mortality and morbidity in aging populations. Uptake of 18-fluorodeoxyglucose (FDG) detected by positron emission tomography (PET) is observed in the wall of 12% of AAA (A+), with most of them being symptomatic. We previously showed that the metabolically active areas displayed adventitial inflammation, medial degeneration and molecular alterations prefacing wall rupture. The aim of this study was to identify new factors predictive of rupture. Transcriptomic analyses were performed in the media and adventitia layers from three types of samples: AAA with-out FDG uptake (A0) and with FDG uptake (A+), both at the positive spot (A+(Pos)) and at a paired distant negative site (A+(Neg)) of the same aneurysm. Follow-up studies included reverse-transcriptase-polymerase chain reaction (RT-PCR), immunohistochemical staining and enzyme-linked immunosorbent assay (ELISA). A large number of genes, including matrix metalloproteinases, collagens and cytokines as well as genes involved in osteochondral development, were differentially expressed in the A+(Pos) compared with A+(Neg). Moreover, a series of genes (notably CCL18) was differentially expressed both in the A+(Neg) and A+(Pos) compared with the A0. A significant increase of CCL18 was also found at the protein level in the aortic wall and in peripheral blood of A+ patients compared with A0. In conclusion, new factors, including CCL18, involved in the progression of AAA and, potentially, in their rupture were identified by a genome-wide analysis of PET-positive and -negative human aortic tissue samples. Further work is needed to study their role in AAA destabilization and weakening.
authors.affiliation: Surgical Research Center, GIGA-Cardiovascular Science Unit, University of Liège, Liège, Belgium.|Laboratory of Connective Tissues Biology, GIGA-Research (GIGA-R), University of Liège, Liège, Belgium.|Department of Cardiovascular and Thoracic Surgery, University Hospital of Liège (CHU), University of Liège, Liège, Belgium.
authors.forename: Audrey
authors.initials: A
authors.lastname: Courtois
authors.affiliation: Laboratory of Connective Tissues Biology, GIGA-Research (GIGA-R), University of Liège, Liège, Belgium.
authors.forename: Betty V
authors.initials: BV
authors.lastname: Nusgens
authors.affiliation: Department of Nuclear Medicine, University Hospital of Liège (CHU), University of Liège, Liège, Belgium.
authors.forename: Roland
authors.initials: R
authors.lastname: Hustinx
authors.affiliation: Department of Nuclear Medicine, University Hospital of Liège (CHU), University of Liège, Liège, Belgium.|Department of Nuclear Medicine, St Joseph Hospital (CHC), Liège, Belgium.
authors.forename: Gauthier
authors.initials: G
authors.lastname: Namur
authors.affiliation: Department of Nuclear Medicine, St Joseph Hospital (CHC), Liège, Belgium.
authors.forename: Pierre
authors.initials: P
authors.lastname: Gomez
authors.affiliation: The Sigfried and Janet Weis Center for Research, Geisinger Health System, Danville, Pennsylvania, United States of America.|Department of Surgery, Temple University School of Medicine, Philadelphia, Pennsylvania, United States of America.
authors.forename: Helena
authors.initials: H
authors.lastname: Kuivaniemi
authors.affiliation: Department of Cardiovascular and Thoracic Surgery, University Hospital of Liège (CHU), University of Liège, Liège, Belgium.
authors.forename: Jean-Olivier
authors.initials: JO
authors.lastname: Defraigne
authors.affiliation: Laboratory of Connective Tissues Biology, GIGA-Research (GIGA-R), University of Liège, Liège, Belgium.
authors.forename: Alain C
authors.initials: AC
authors.lastname: Colige
authors.affiliation: Surgical Research Center, GIGA-Cardiovascular Science Unit, University of Liège, Liège, Belgium.|Department of Nuclear Medicine, University Hospital of Liège (CHU), University of Liège, Liège, Belgium.
authors.forename: Natzi
authors.initials: N
authors.lastname: Sakalihasan
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001012:Aorta, Abdominal / Q000378:metabolism; D017544:Aortic Aneurysm, Abdominal / Q000235:genetics* / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D019742:Chemokines, CC / Q000235:genetics* / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D049268:Positron-Emission Tomography; D012306:Risk; D059467:Transcriptome
chemical_list: D015415:Biomarkers; C111792:CCL18 protein, human; D019742:Chemokines, CC