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Molecular Medicine

, Volume 20, Issue 1, pp 697–706 | Cite as

Gene Expression Study in Positron Emission Tomography-Positive Abdominal Aortic Aneurysms Identifies CCL18 as a Potential Biomarker for Rupture Risk

  • Audrey Courtois
  • Betty V. Nusgens
  • Roland Hustinx
  • Gauthier Narnur
  • Pierre Gomez
  • Helena Kuivaniemi
  • Jean-Olivier Defraigne
  • Alain C. Colige
  • Natzi Sakalihasan
Research Article

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 without 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 AO. 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.

Notes

Acknowledgments

We thank the surgeons and nurses of the Department of Cardiovascular and Thoracic Surgery of the CHU of Liège, the CHC St Joseph and CHR Citadelle for their contribution to the collection of AAA specimens. We thank Benoit Hennuy and the GenoTranscriptomics platform of the GIGA for carrying out the microarray experiments. We thank Joan Somja for analysis of the histological sections. This work was supported by the FP7 European Program Fighting Aneurysmal Diseases number 200647, the Belgian Fonds de la Recherche Scientifique (grant 3.4518.07) and a grant from the University of Liège.

Supplementary material

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Supplementary material, approximately 562 KB.

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Authors and Affiliations

  • Audrey Courtois
    • 1
    • 2
    • 3
  • Betty V. Nusgens
    • 2
  • Roland Hustinx
    • 4
  • Gauthier Narnur
    • 4
    • 5
  • Pierre Gomez
    • 5
  • Helena Kuivaniemi
    • 6
    • 7
  • Jean-Olivier Defraigne
    • 3
  • Alain C. Colige
    • 2
  • Natzi Sakalihasan
    • 1
    • 4
  1. 1.Surgical Research Center, GIGA-Cardiovascular Science UnitUniversity of LiègeLiègeBelgium
  2. 2.Laboratory of Connective Tissues Biology, GIGA-Research (GIGA-R)University of LiègeLiègeBelgium
  3. 3.Department of Cardiovascular and Thoracic SurgeryUniversity Hospital of Liège (CHU), University of LiègeLiègeBelgium
  4. 4.Department of Nuclear MedicineUniversity Hospital of Liège (CHU), University of LiègeLiègeBelgium
  5. 5.Department of Nuclear MedicineSt Joseph Hospital (CHC)LiègeBelgium
  6. 6.The Sigfried and Janet Weis Center for ResearchGeisinger Health SystemDanvilleUSA
  7. 7.Department of SurgeryTemple University School of MedicinePhiladelphiaUSA

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