18F-FDG Uptake Assessed by PET/CT in Abdominal Aortic Aneurysms Is Associated with Cellular and Molecular Alterations Prefacing Wall Deterioration and Rupture
18F-FDG Uptake Assessed by PET/CT in Abdominal Aortic Aneurysms Is Associated with Cellular and Molecular Alterations Prefacing Wall Deterioration and Rupture
复制标题
DOI：
10.2967/jnumed.112.115873
复制
发表时间：
2013-10-01
影响因子：
9.3
通讯作者：
Sakalihasan, Natzi
中科院分区：
文献类型：
--
作者：
Courtois, Audrey;Nusgens, Betty V.;Sakalihasan, Natzi
腹主动脉瘤破裂是老年人群中一个重要的并发症和死亡率，其预测将是最有益的公共卫生。在12%的AAA患者（PET+）中发现PET检测到的F-18-FDG摄取阳性斑点，这些患者通常有症状且具有高破裂风险。将F-18-FDG阳性部位与同一动脉瘤的阴性部位以及从没有F-18-FDG吸收的AAA患者中收集的样本进行比较，应该可以区分生物学变化，这将有助于识别预测破裂的标记物。研究方法：从无F-18-FDG摄取的患者（PET 0，n = 10）和PET 1患者（n = 8）中获得AAA壁的活检，均在摄取阳性的部位和远端的阴性部位。通过免疫组织化学、定量实时聚合酶链反应和酶谱法对样本进行分析。结果如下：具有阳性F-18-FDG摄取的平滑肌壁的位点的特征在于外膜炎性细胞的数量显著增加，高度增殖，并且与它们的阴性对应物和PET 0壁相比，介质中平滑肌细胞（SMC）急剧减少。与PET 0壁相比，PET+阴性位点中参与壁的维持和重塑的一系列基因的表达被显著修饰，表明血管壁的系统性改变。此外，几种基质金属蛋白酶（MMPs），特别是MMP 1和MMP 13胶原酶，在阳性部位，主要是在外膜中观察到显着增加。此外，PET+患者的特征是较高的循环C反应蛋白。结论：血管壁F-18-FDG阳性摄取与活跃的炎症过程相关，其特征为外膜中增殖白细胞的密集浸润和循环C-反应蛋白的增加。此外，中膜中SMC的丢失和参与外膜重塑和胶原降解的基因表达的改变可能参与破裂前血管壁的弱化。
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 F-18-FDG detected by PET are found in 12% of AAA patients (PET+), who are most often symptomatic and at high rupture risk. Comparing the F-18-FDG-positive site with a negative site from the same aneurysm and with samples collected from AAA patients with no F-18-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 F-18-FDG uptake (PET0, n = 10) and from PET1 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 F-18-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 F-18-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.