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 (PET1), 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 5 10) and from PET1 patients (n 5 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 PET1, 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, PET1 patients were characterized by a higher circulating C-reactive protein. Conclusion: 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.
these data suggest a possible association between increased 18-FDG uptake and AAA expansion and rupture.
These preliminary observations point to a potential link between high wall stress and accelerated metabolism in aortic aneurysm wall and warrant further large population-based studies.
A neurysms are permanent vascular dilatations that involve the aorta in ≤10% of subjects >65 years of age, with more than half localized in the infrarenal aorta.1,2 Their rupture causes death in ≤90% of cases, 2,3 and according to recent trials, the operative mortality does not exceed 5%. 4 The aneurysm maximal diameter identifies the time point when the risk of rupture exceeds that of repair, hence indicating a preventive intervention in asymptomatic patients. [5][6][7] Research, however, has been driven toward more patient-specific risk assessment because aneurysms above the critical diameter thresholds may never rupture, whereas smaller aneurysms will. 8-10 Clinical Perspective on p 91Rupture occurs when the wall stress exceeds the wall strength. Aortic geometry can be used for finite element simulations (FES) 11,12 providing, among other estimates, wall stress. Before rupture occurs, wall stress is involved in aneurysmal expansion and remodeling; the latter triggers and amplifies numerous biological mechanisms that may result in apposition of an intraluminal thrombus with its own biomechanical 13 and biological characteristics. [14][15][16][17] The biological activity of the aortic wall can be evaluated indirectly through energy consumption using 18 F-fluoro-deoxy-glucose ( 18 F-FDG) as a tracer for positron emission tomographic (PET) imaging. 18 18 F-FDG uptake is not uncommon in aortic aneurysms 19,20 and has been shown to correlate with the amount of inflammatory cells, proteolytic activity, and risk of rupture. [21][22][23] Xu et al 24 previously evidenced associations among biological activity, wall stress estimates, and rupture in 3 patients with aortic aneurysms. The actual relationship between biomechanical parameters and biological activity, however, has never been studied in large series.Our study was designed to assess the relationship and the independent determinants between biomechanical estimates of wall stress and 18 F-FDG uptake in unruptured aortic aneurysms. The mean number of these areas per examination was 1.6 (18 of 11) in thoracic aortic aneurysms versus 0.25 (14 of 57) in abdominal aortic aneurysms, whereas the mean number of increased uptake areas colocalizing with highest wall stress and stress/strength index areas was 0.55 (6 of 11) and 0.02 (1 of 57), respectively. Quantitatively, 18 F-FDG positron emission tomographic uptake correlated positively with both wall stress and stress/strength index (P<0.05). Background-The18 F-FDG uptake was particularly high in subjects with personal history of angina pectoris and familial aneurysm. Conclusions-Increased Methods Study PatientsThis study is part of a larger trial aiming to determine the role of 18 F-FDG PET in aortic aneurysm rupture risk assessment as approved by the institutional review board. 25 It included 53 patients (45 men) with aortic aneurysm who underwent ≥1 whole-body 18 F-FDG PET examination using contrast-enhanced computed tomography (CT) for attenuation correction in a single center within a 5-year period. All pat...
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