COLLAGENASES AND ABDOMINAL AORTIC ANEURYSMS

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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.