Diehm Nicolas, Di Santo Stefano, Schaffner Thomas, Schmidli Juerg, Völzmann Jan, Jüni Peter, Baumgartner Iris, Kalka Christoph
Division of Clinical and Interventional Angiology, Swiss Cardiovascular Center, University Hospital Bern, Bern, Switzerland.
J Vasc Surg. 2008 Aug;48(2):425-34. doi: 10.1016/j.jvs.2008.03.001. Epub 2008 May 23.
The success of open and endovascular repair of abdominal aortic aneurysms (AAA) is hampered by postoperative dilatation of the anatomical neck of the AAA, which is used for graft attachment. The purpose of this study was to determine whether the macroscopically non-diseased infrarenal aortic neck of AAA is histologically and biochemically altered at the time of operative repair.
We harvested full-thickness aortic wall samples as longitudinal stripes spanning from AAA neck to aneurysmal sac in 22 consecutive patients undergoing open surgical AAA repair. Control tissue was obtained from five organ donors and five deceased subjects undergoing autopsy without evidence of aneurysmal disease. We assessed aortic media thickness, number of intact elastic lamellar units, media destruction, and neovascularization grade and performed immunohistochemistry for matrix metalloproteinase (MMP)-9 and phosphorylated c-Jun N-terminal kinase (p-JNK). MMP-9 and p-JNK protein expressions were quantified using Western Blots.
The median thickness of the aortic media was 1150 mum in control tissue (range, 1000-1300), 510 mum in aortic necks (250-900), and 200 mum in aortic sacs (50-500, P from nonparametric test for trend <.001). The number of intact elastic lamellar units was 33 in controls (range, 33-55), 12 in aortic necks (0-31) and three in aortic sacs (0-10, P < .001). The expression of MMP-9 and p-JNK as assessed by Western Blots (P = .007 and .061, respectively) and zymography (P for trend <.001) were up regulated in both the AAA neck and sac compared with controls. Except for p-JNK expression, differences between tissues were similar after the adjustment for age, gender, and type of sampling.
The seemingly non-diseased infrarenal AAA neck in patients with AAA undergoing surgical repair shows histological signs of destruction and upregulation of potential drug targets.
腹主动脉瘤(AAA)开放修复和血管腔内修复的成功受到用于移植物附着的AAA解剖颈部术后扩张的阻碍。本研究的目的是确定在手术修复时,AAA宏观上无病变的肾下主动脉颈部在组织学和生物化学上是否发生改变。
我们从22例接受开放手术AAA修复的连续患者中获取了全层主动脉壁样本,样本为从AAA颈部到动脉瘤囊的纵向条带。对照组织取自5名器官捐赠者和5名无动脉瘤疾病证据的尸检死者。我们评估了主动脉中膜厚度、完整弹性层单位数量、中膜破坏和新生血管化程度,并对基质金属蛋白酶(MMP)-9和磷酸化c-Jun氨基末端激酶(p-JNK)进行了免疫组织化学检测。使用蛋白质印迹法对MMP-9和p-JNK蛋白表达进行定量。
对照组织中主动脉中膜的中位数厚度为1150μm(范围1000 - 1300),主动脉颈部为510μm(250 - 900),主动脉囊为200μm(50 - 500,非参数趋势检验P <.001)。完整弹性层单位数量在对照组为33个(范围33 - 55),主动脉颈部为12个(0 - 31),主动脉囊为3个(0 - 10,P <.001)。与对照组相比,AAA颈部和囊中的MMP-9和p-JNK表达通过蛋白质印迹法评估(分别为P =.007和.061)以及酶谱法(趋势P <.001)均上调。除p-JNK表达外,在对年龄、性别和采样类型进行调整后,组织之间的差异相似。
接受手术修复的AAA患者中看似无病变的肾下AAA颈部显示出组织学破坏迹象和潜在药物靶点的上调。