Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
Atherosclerosis. 2011 Oct;218(2):294-9. doi: 10.1016/j.atherosclerosis.2011.05.002. Epub 2011 May 11.
Rupture of an abdominal aortic aneurysm (AAA) is the cause of death in approximately 2% of men above 65 years. Most AAAs contain an intra-luminal thrombus (ILT), which is a potential source of proteases capable of degrading the underlying aneurysm wall. The AAA wall covered by a thick ILT shows more signs of matrix degradation compared to the wall free from ILT. The purpose of the present study was to evaluate the presence of protease activity in the ILT.
ILT and peripheral blood from 32 patients undergoing elective surgery were collected. The ILT was divided into abluminal, luminal, and a middle layer in between. Collagenases, gelatinases, elastase, and their inhibitors were measured using ELISA in protein extracts from these layers. Immunohistochemistry was used for identification of cells.
Neutrophil leukocytes and platelets were mostly detected in the luminal layer of the ILT. MMP-9 and neutrophil elastase were also abundant in this layer but with low activity. High concentrations of TIMP-1 and PAI-1 were detected in the abluminal layer, while alpha 1 antitrypsin was mostly found in the luminal layer of the ILT.
In AAA thick ILTs with multiple layers contain substantial amounts of proteases, but their activity is limited to the luminal layer. Proteases in the abluminal layer are mostly inactive, probably due to excess amounts of inhibitors and are consequently unable to directly participate in the pathogenesis of AAA.
腹主动脉瘤（AAA）破裂是导致 65 岁以上男性死亡的原因之一，约占 2%。大多数 AAA 包含一个腔内血栓（ILT），这是一种潜在的蛋白酶来源，能够降解潜在的动脉瘤壁。与无 ILT 的壁相比，覆盖有厚 ILT 的 AAA 壁显示出更多的基质降解迹象。本研究的目的是评估 ILT 中蛋白酶活性的存在。
收集 32 名接受择期手术的患者的 ILT 和外周血。将 ILT 分为外膜、内膜和中间层。使用 ELISA 测量来自这些层的蛋白质提取物中的胶原酶、明胶酶、弹性蛋白酶及其抑制剂。免疫组织化学用于鉴定细胞。
中性粒细胞白细胞和血小板主要存在于 ILT 的内膜层。MMP-9 和中性粒细胞弹性蛋白酶在这个层中也很丰富，但活性较低。TIMP-1 和 PAI-1 的高浓度在无内膜层中被检测到，而α 1 抗胰蛋白酶主要存在于 ILT 的内膜层。
在具有多层的 AAA 厚 ILT 中，含有大量的蛋白酶，但它们的活性仅限于内膜层。无内膜层中的蛋白酶大多处于非活性状态，可能是由于抑制剂的过量，因此无法直接参与 AAA 的发病机制。
