Ando T, Nagai K, Chikada M, Okamoto K, Kurokawa M, Kobayashi T, Kato T, Makuuchi H
Department of Cardiovascular Surgery, St. Marianna University School of Medicine, Kawasaki, Japan.
J Cardiovasc Surg (Torino). 2011 Aug;52(4):545-55.
The mechanisms underlying the formation of abdominal aortic aneurysms have yet to be fully clarified. To identify key proteins generally involved in aneurysmal formation, proteomic profiles were compared between aneurysmal and non-aneurysmal regions of aortic walls from patients with abdominal aortic aneurysm.
Aortic wall specimens were obtained from three patients with abdominal aortic aneurysm. Protein profiles of aortic wall samples including vascular media and adventitia were compared between aneurysmal and non-aneurysmal regions in each patient using two-dimensional fluorescence difference gel electrophoresis (2D-DIGE). Protein spots expressed differently between the two regions were identified by tandem mass spectrometry and verified by immunohistochemical investigations.
Image analysis of 2D-DIGE gels revealed 22 proteins spots expressed differently between aneurysmal and non-aneurysmal regions in all three patients. Among these, five protein spots that were up-regulated in the AA regions were successfully identified as complement component C4, fragments of the fibrinogen alpha or beta subunits, and actin. Immunohistochemical studies showed massive deposition of fibrin/fibrinogen or its fragments in the media, and complement C1q component, the molecule starting the classical complement pathway, in all three layers of the aneurysmal region.
Our proteomic and subsequent immunohistochemical studies revealed significant fibrinogenesis and fibrinolysis in the media, and activation of the classical complement pathway in all three layers of the aneurysmal region. These data promote understanding of mechanisms behind the formation of abdominal aortic aneurysms.
腹主动脉瘤形成的潜在机制尚未完全阐明。为了确定通常参与动脉瘤形成的关键蛋白质，对腹主动脉瘤患者主动脉壁的动脉瘤区域和非动脉瘤区域的蛋白质组图谱进行了比较。
从三名腹主动脉瘤患者获取主动脉壁标本。使用二维荧光差异凝胶电泳（2D-DIGE）比较每位患者动脉瘤区域和非动脉瘤区域的主动脉壁样本（包括血管中膜和外膜）的蛋白质图谱。通过串联质谱法鉴定两个区域之间差异表达的蛋白质斑点，并通过免疫组织化学研究进行验证。
2D-DIGE凝胶的图像分析显示，所有三名患者的动脉瘤区域和非动脉瘤区域之间有22个蛋白质斑点差异表达。其中，在动脉瘤区域上调的五个蛋白质斑点被成功鉴定为补体成分C4、纤维蛋白原α或β亚基的片段以及肌动蛋白。免疫组织化学研究显示，在动脉瘤区域的所有三层中，纤维蛋白/纤维蛋白原或其片段大量沉积，以及经典补体途径起始分子补体C1q成分。
我们的蛋白质组学及后续免疫组织化学研究揭示了中膜显著的纤维蛋白生成和纤维蛋白溶解，以及动脉瘤区域所有三层中经典补体途径的激活。这些数据有助于理解腹主动脉瘤形成背后的机制。
