18F-FDG Uptake Assessed by PET/CT in Abdominal Aortic Aneurysms Is Associated with Cellular and Molecular Alterations Prefacing Wall Deterioration and Rupture

Autor: Natzi Sakalihasan, Philippe Delvenne, Jean-Baptiste Michel, Joan Somja, Jean-Olivier Defraigne, Audrey Courtois, Alain Colige, Gauthier Namur, Pierre Gomez, Roland Hustinx, Betty Nusgens
Rok vydání: 2013
Předmět:
Male
Pathology
medicine.medical_specialty
MMP1
Aortic Rupture
030204 cardiovascular system & hematology
Matrix metalloproteinase
Multimodal Imaging
03 medical and health sciences
0302 clinical medicine
Aneurysm
Fluorodeoxyglucose F18
Adventitia
Leukocytes
medicine
Humans
Radiology
Nuclear Medicine and imaging
Zymography
Aorta
Abdominal
cardiovascular diseases
Aged
Aged
80 and over
PET-CT
business.industry
Gene Expression Profiling
Biological Transport
Prognosis
medicine.disease
3. Good health
Enzyme Activation
medicine.anatomical_structure
Matrix Metalloproteinase 9
Positron-Emission Tomography
030220 oncology & carcinogenesis
cardiovascular system
Collagenase
Matrix Metalloproteinase 2
Immunohistochemistry
Female
Tomography
X-Ray Computed
business
Biomarkers
Aortic Aneurysm
Abdominal
medicine.drug
Zdroj: Journal of Nuclear Medicine; Vol 54
ISSN: 2159-662X
0161-5505
Popis: 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 18F-FDG detected by PET are found in 12% of AAA patients (PET+), who are most often symptomatic and at high rupture risk. Comparing the 18F-FDG–positive site with a negative site from the same aneurysm and with samples collected from AAA patients with no 18F-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 18F-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 18F-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. Conclusion: Positive 18F-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.
Databáze: OpenAIRE
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