腹主动脉瘤壁中的半胱氨酸蛋白酶活性。

Cysteine protease activity in the wall of abdominal aortic aneurysms.

作者信息

Abisi Said, Burnand Kevin G, Waltham Matthew, Humphries Julia, Taylor Peter R, Smith Alberto

机构信息

Academic Department of Surgery, Cardiovascular Division, King's College School of Medicine, St Thomas' Hospital, London, United Kingdom.

出版信息

J Vasc Surg. 2007 Dec;46(6):1260-6. doi: 10.1016/j.jvs.2007.08.015.

DOI:10.1016/j.jvs.2007.08.015

PMID:18155003

Abstract

BACKGROUND

Cysteine proteases are potent elastolytic enzymes and together with their inhibitor, cystatin C, have been linked with the growth of abdominal aortic aneurysms (AAAs). These enzymes and their inhibitors have previously been studied in AAAs, but comparisons have always been made with wall from normal aorta. Atherosclerosis is a feature of aneurysmal disease and may therefore confound comparisons with normal wall. This study compared the expression and activity of cysteine proteases and their inhibitors in aneurysm wall with their expression in the aortic wall of patients with aortic occlusive disease (AOD).

METHODS

Aortic wall was obtained from 82 patients with AAA and 13 with AOD. Protein expression and activity of cathepsin B, H, K, L and S, and cystatins A, B, and C were measured by enzyme-linked immunosorbent assay and specific fluorogenic substrate assays. Matrix metalloproteinase 9 (MMP-9) activity was measured by quantitative bioimmunoassay in the same extracts.

RESULTS

AAA wall had 330% more cathepsin H protein (P = .007) and >30% less cystatin C (P = .03) than the aortic wall from patients with AOD. The activity of cathepsins B, H, L, and S was significantly greater in AAA than AOD (376%, [P < .0001], 191%, [P = 0.019], 223%, P = 0.002, and approximately 20% [P = 0.045] respectively). MMP-9 activity was also increased in AAA compared with AOD (P<0.0001) and levels in the wall of AAA correlated positively with cathepsin L activity (r = 0.42, P<.0001) and negatively with cystatin C (r = -0.75, P<.0001).

CONCLUSIONS

The activity of four cathepsins B, H, L, and S was higher in the aneurysm wall than in aortic wall of patients with occlusive disease. This was associated with a reduced level of cystatin C in the aneurysmal wall. Cathepsin H was the only protein in which there was a correlation between protein level and activity, which suggests that post-translational modifications were responsible for activation of the other cathepsins. Increased cathepsin activity may influence the activity of MMP-9, which is thought to have an important role in aneurysm development.

摘要

背景

半胱氨酸蛋白酶是强效的弹性蛋白酶，与其抑制剂胱抑素C一起，与腹主动脉瘤（AAA）的生长有关。此前已对这些酶及其抑制剂在AAA中进行过研究，但一直是与正常主动脉壁进行比较。动脉粥样硬化是动脉瘤疾病的一个特征，因此可能会混淆与正常壁的比较。本研究比较了半胱氨酸蛋白酶及其抑制剂在动脉瘤壁中的表达和活性与在主动脉闭塞性疾病（AOD）患者主动脉壁中的表达和活性。

方法

从82例AAA患者和13例AOD患者获取主动脉壁。通过酶联免疫吸附测定和特异性荧光底物测定法测量组织蛋白酶B、H、K、L和S以及胱抑素A、B和C的蛋白表达和活性。在相同提取物中通过定量生物免疫测定法测量基质金属蛋白酶9（MMP-9）的活性。

结果

与AOD患者的主动脉壁相比，AAA壁中的组织蛋白酶H蛋白多330%（P = 0.007），胱抑素C少30%以上（P = 0.03）。AAA中组织蛋白酶B、H、L和S的活性显著高于AOD（分别为376%，[P < 0.0001]，191%，[P = 0.019]，223%，P = 0.002，和约20% [P = 0.045]）。与AOD相比，AAA中的MMP-9活性也增加（P < 0.0001），AAA壁中的水平与组织蛋白酶L活性呈正相关（r = 0.42，P < 0.0001），与胱抑素C呈负相关（r = -0.75，P < 0.0001）。