COLLAGENASES AND ABDOMINAL AORTIC ANEURYSMS

腹主动脉瘤的患病率在普通人群中约为1.5%至4%。未经治疗的腹主动脉瘤的自然病史是进行性增大，最终破裂或血栓栓塞性并发症。主动脉壁弹性蛋白和胶原纤维的降解会导致抗张强度降低和动脉瘤扩张。胶原蛋白的破坏很可能是由间质胶原酶介导的，间质胶原酶是基质金属蛋白酶家族(MMP1和MMP13)的成员。我们建议研究基质金属蛋白酶-1和基质金属蛋白酶-13在腹主动脉瘤发生发展中的作用。用免疫印迹法检测主动脉蛋白提取液中基质金属蛋白酶-1和基质金属蛋白酶-13的表达。这些酶及其相应的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。利用竞争性逆转录聚合酶链式反应，我们将量化正常和病变主动脉中胶原酶mRNA表达的差异。我们将检查已知的MMPs抑制剂多西环素治疗是否抑制AAA中基质金属蛋白酶-1和基质金属蛋白酶13的表达。我们研究的长期目标是进一步描述AAA中基质降解的过程，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.