Vascular Research Laboratory, Fundación Jiménez Diaz-Instituto de Investigaciones Sanitarias, Autonoma University, Av Reyes Católicos 2, 28040 Madrid, Spain.
Arterioscler Thromb Vasc Biol. 2011 Dec;31(12):3011-9. doi: 10.1161/ATVBAHA.111.237537. Epub 2011 Sep 22.
Polymorphonuclear neutrophils (PMNs) play a main role in abdominal aortic aneurysm (AAA) progression. We have analyzed circulating PMNs isolated from AAA patients and controls by a proteomic approach to identify proteins potentially involved in AAA pathogenesis.
PMNs from 8 AAA patients (4 large AAA >5 cm and 4 small AAA 3-5 cm) and 4 controls were analyzed by 2D differential in-gel electrophoresis. Among differentially expressed spots, several proteins involved in redox balance were identified by mass spectrometry (eg, cyclophilin, thioredoxin reductase, catalase). Diminished catalase expression and activity were observed in PMNs from AAA patients compared with controls. In contrast, PMNs from AAA patients displayed higher H(2)O(2) and myeloperoxidase levels than PMNs from controls. Moreover, a significant decrease in catalase mRNA levels was observed in PMNs after phorbol 12-myristate 13-acetate incubation. Catalase plasma levels were also decreased in large (n=47) and small (n=56) AAA patients compared with controls (n=34). We observed catalase expression in AAA thrombus and thrombus-conditioned medium, associated with PMN infiltration. Furthermore, increased H(2)O(2) levels were observed in AAA thrombus-conditioned medium compared with the media layer.
Diminished catalase levels in circulating PMNs and plasma are observed in AAA patients, supporting an important role of oxidative stress in AAA evolution.
多形核粒细胞（PMN）在腹主动脉瘤（AAA）进展中起主要作用。我们通过蛋白质组学方法分析了从 AAA 患者和对照者中分离的循环 PMN，以鉴定可能参与 AAA 发病机制的蛋白。
通过二维差异凝胶电泳分析了 8 名 AAA 患者（4 名大 AAA >5 cm 和 4 名小 AAA 3-5 cm）和 4 名对照者的 PMN。通过质谱鉴定了几个涉及氧化还原平衡的差异表达斑点（如亲环蛋白、硫氧还蛋白还原酶、过氧化氢酶）。与对照者相比，AAA 患者的 PMN 中过氧化氢酶表达和活性降低。相反，与对照者相比，AAA 患者的 PMN 显示出更高的 H₂O₂和髓过氧化物酶水平。此外，在佛波醇 12-肉豆蔻酸 13-乙酸孵育后，观察到 PMN 中的过氧化氢酶 mRNA 水平显著降低。与对照者相比，大 AAA（n=47）和小 AAA（n=56）患者的过氧化氢酶血浆水平也降低。我们观察到在 AAA 血栓和血栓条件培养基中存在过氧化氢酶表达，与 PMN 浸润有关。此外，与介质层相比，在 AAA 血栓条件培养基中观察到更高的 H₂O₂水平。
在 AAA 患者中观察到循环 PMN 和血浆中的过氧化氢酶水平降低，支持氧化应激在 AAA 演变中的重要作用。
