COLLAGENASES AND ABDOMINAL AORTIC ANEURYSMS

在一般人群中，腹主动脉瘤的患病率约为1.5%至4%。未经治疗的AAA的自然历史是进行性扩大，最终破裂或血栓栓塞并发症。主动脉壁弹性蛋白和胶原纤维的降解导致抗张强度降低和动脉瘤扩张。胶原破坏最有可能是由基质金属蛋白酶家族成员（MMP-1和MMP-13）间质胶原酶介导的。我们建议研究MMP-1和MMP-13在AAA发展中的作用。Western blotting检测主动脉蛋白提取物中MMP-1和MMP-13的表达。这些酶及其相应mRNA的组织分布将分别通过免疫组织化学和原位杂交技术进行检测。使用竞争性逆转录酶聚合酶链反应，我们将量化正常与病变主动脉中胶原酶mRNA表达的差异。我们将研究用多西环素（一种已知的MMPs抑制剂）治疗是否会抑制AAA中MMP-1和MMP-13的表达。我们研究的长期目标是进一步表征AAA中基质降解过程，并研究抑制基质破坏的方法。

The prevalence of abdominal aortic aneurysms is about 1.5 to 4 percent in the general population. The natural history of untreated AAA is of progressive enlargement with eventual rupture or thromboembolic complications. Degradation of aortic wall elastin and collagen fibers results in diminished tensile strength and aneurysmal dilatation. Collagen destruction most likely is mediated by the interstitial collagenases, members of the matrix metalloproteinase family (MMP-1 and MMP-13). We propose to investigate the role of MMP-1 and MMP-13 in AAA development. Expression of MMP-1 and MMP-13 in aortic protein extracts will be examined by Western blotting. Tissue distribution of these enzymes and their corresponding mRNA will be examined by immunohistochemistry and in situ hybridization techniques, respectively. Using competitive reverse transcriptase polymerase chain reaction, we will quantify differences in collagenase mRNA expression in normal versus diseased aortas. We will examine whether treatment with doxycycline, a known inhibitor of MMPs, inhibits expression of MMP-1 and MMP-13 in AAA. The long term goal of our research is to further characterize matrix degrading processes in AAA and to investigate methods for inhibiting matrix destruction.