Department of Vascular and Endovascular Surgery, University Hospital Heidelberg, D-69120 Heidelberg, Germany.
Neurology Department, University Hospital Heidelberg, D-69120 Heidelberg, Germany.
Int J Mol Med. 2019 Oct;44(4):1299-1308. doi: 10.3892/ijmm.2019.4307. Epub 2019 Aug 7.
Abdominal aortic aneurysms (AAAs) are characterized by chronic inflammatory cell infiltration. The present extended immunohistochemistry study aimed to characterize inflammation in AAA and aortic control samples. In specific, the composition of the infiltrating immune cells and the expression of five inflammasome components in these immune cells were evaluated, in order to characterize their role in AAA development. A total of 104 biopsies from 48 AAA patients and 40 healthy specimens from organ donors were evaluated for their grade of inflammation. Infiltrating leukocytes were characterized by specific markers (CD3, CD20 and CD68), intramural localization and inflammasome protein expression [NLR family pyrin domain containing 3 (NLRP3), absent in melanoma 2 (AIM2), apoptosis‑associated speck‑like protein containing a caspase recruitment domain (ASC), Caspase‑1 and Caspase‑5]. Macrophages, B and T lymphocytes were detected to a similar extent in grade 1, 2 and 3 AAA specimens, whereas in control samples, B and T lymphocytes were rarely observed in grade 1 lesions. Expression frequencies of NLRP3, AIM2 and Caspase‑5 were significantly higher in grade 1 lesions of AAA samples compared with grade 1 lesions in control samples. Finally, AIM2, ASC, and Caspase‑5 displayed significantly lower expression frequencies in grade 3 compared with grade 2 AAA specimens, and all inflammasome components were less frequently detected in grade 3 than in grade 1 lesions of AAA. This indicates that inflammasome activities decrease with AAA progression in infiltrating leukocytes. No statistically significant association was found for grade 2 and grade 3 lesions and total leukocyte count, C‑reactive protein levels, maximal aortic diameter, plasma cholesterol level or biomechanical parameters (derived from finite element analysis) of the respective patients. Overall, the aortic wall of AAA contained lymphocytes and macrophages with different states of activity. The present data suggested that therapeutic inhibition of specific inflammasome components might counteract AAA development and progression.
腹主动脉瘤（AAA）的特征是慢性炎症细胞浸润。本扩展免疫组织化学研究旨在描述 AAA 和主动脉对照样本中的炎症。具体而言，评估了浸润免疫细胞的组成和这些免疫细胞中五种炎症小体成分的表达，以确定它们在 AAA 发展中的作用。评估了 48 名 AAA 患者的 104 个活检标本和 40 名器官捐献者的健康对照标本的炎症程度。浸润白细胞用特异性标记物（CD3、CD20 和 CD68）、壁内定位和炎症小体蛋白表达（NLR 家族包含 pyrin 结构域的 3（NLRP3）、黑色素瘤 2 缺失（AIM2）、凋亡相关斑点样蛋白包含半胱氨酸蛋白酶募集结构域（ASC）、Caspase-1 和 Caspase-5）进行了描述。巨噬细胞、B 和 T 淋巴细胞在 1、2 和 3 级 AAA 标本中的检出程度相似，而在对照标本中，1 级病变中很少观察到 B 和 T 淋巴细胞。与对照样本的 1 级病变相比，NLRP3、AIM2 和 Caspase-5 在 AAA 样本的 1 级病变中的表达频率明显更高。最后，与 2 级 AAA 标本相比，AIM2、ASC 和 Caspase-5 在 3 级 AAA 标本中的表达频率明显降低，与 AAA 的 1 级病变相比，3 级病变中所有炎症小体成分的检出频率均较低。这表明炎症小体活性在浸润白细胞中随着 AAA 的进展而降低。在 2 级和 3 级病变以及总白细胞计数、C 反应蛋白水平、最大主动脉直径、血浆胆固醇水平或各自患者的生物力学参数（源自有限元分析）之间未发现统计学上显著关联。总体而言，AAA 的主动脉壁包含具有不同活性状态的淋巴细胞和巨噬细胞。本研究数据表明，针对特定炎症小体成分的治疗性抑制可能会抑制 AAA 的发展和进展。
Zotero 插件
