Wu Xiaoyu, Cakmak Sinan, Wortmann Markus, Hakimi Maani, Zhang Jian, Böckler Dittmar, Dihlmann Susanne
Department of Vascular & Thyroid Surgery, The First Hospital of China Medical University, Nanjing North Street 155, 110001 Shenyang, China.
University Hospital Heidelberg, Department of vascular and endovascular surgery, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany.
Mol Med. 2016 Oct;22:505-518. doi: 10.2119/molmed.2016.00035. Epub 2016 Jul 29.
Male sex is a risk factor for abdominal aortic aneurysm (AAA). Within the AAA adventitia, infiltrating leukocytes express high levels of inflammasome components. To further elucidate the role of inflammatory cells in the pathogenesis of AAA, we here addressed expression and functionality of inflammasome components in peripheral blood mononuclear cells (PBMC) of AAA patients in association with sex. PBMC and plasma were isolated from 100 vascular patients, including 34 pairs of AAA patients and age/sex-matched non-AAA patients. Male PBMC were found to express significantly higher mRNA levels of , and (all < 0.0001) than female PBMC. Within the male patients, PBMC of AAA patients displayed increased mRNA levels of and ( = 0.0004) compared to matched non-AAA PBMC, whereas there was no difference between female AAA and non-AAA patients. The relative protein level of NLRP3 was significantly lower in PBMC lysates from all AAA patients than in matched controls ( = 0.038), whereas AIM2 and active Caspase-1 (p10) protein levels were significantly increased ( = 0.014 and = 0.049). ELISA revealed significantly increased IL-1α (mean = 6.34 vs 0.01 pg/ml) and IL-1β plasma levels (mean = 12.07 vs. 0.04 pg/ml) in AAA patients. The data indicate that male PBMC display a systemic proinflammatory state with primed inflammasomes that may contribute to AAA-pathogenesis. The AAA-specific inflammasome activation pattern suggests differential regulation of the sensors AIM2 and NLRP3 in inflammatory cells of AAA patients.
男性是腹主动脉瘤（AAA）的一个危险因素。在AAA外膜中，浸润的白细胞表达高水平的炎性小体成分。为了进一步阐明炎症细胞在AAA发病机制中的作用，我们在此研究了AAA患者外周血单个核细胞（PBMC）中炎性小体成分的表达及其功能与性别的关系。从100名血管疾病患者中分离出PBMC和血浆，其中包括34对AAA患者以及年龄/性别匹配的非AAA患者。发现男性PBMC中 、 和 的mRNA水平显著高于女性PBMC（均P<0.0001）。在男性患者中，与匹配的非AAA患者的PBMC相比，AAA患者的PBMC中 和 的mRNA水平升高（P = 0.0004），而女性AAA患者和非AAA患者之间则没有差异。所有AAA患者的PBMC裂解物中NLRP3的相对蛋白水平显著低于匹配的对照组（P = 0.038），而AIM2和活性半胱天冬酶-1（p10）的蛋白水平显著升高（P = 0.014和P = 0.049）。ELISA显示AAA患者血浆中IL-1α（平均值= 6.34 vs 0.01 pg/ml）和IL-1β水平显著升高（平均值= 12.07 vs. 0.04 pg/ml）。数据表明，男性PBMC呈现系统性促炎状态，炎性小体处于预激活状态，这可能有助于AAA的发病机制。AAA特异性炎性小体激活模式表明，AAA患者炎症细胞中传感器AIM2和NLRP3受到不同的调节。
