COLLAGENASES AND ABDOMINAL AORTIC ANEURYSMS

胶原酶和腹主动脉瘤

• 批准号: 6182827
• 负责人: JASON K LEE
• 金额: $ 3.89万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-21 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6182827
• 关键词: aorta aneurysm; artery occlusion; collagenase; histopathology; human tissue

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.

腹主动脉瘤的患病率在一般人群中约为1.5%至4%。 未经治疗的腹主动脉瘤的自然病程是进行性增大，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间质胶原酶介导的，间质胶原酶是基质金属蛋白酶家族的成员（MMP-1和MMP-13）。 我们建议研究MMP-1和MMP-13在AAA发展中的作用。 通过蛋白质印迹法检测主动脉蛋白提取物中MMP-1和MMP-13的表达。 将分别通过免疫组织化学和原位杂交技术检查这些酶及其相应mRNA的组织分布。 利用竞争性逆转录聚合酶链反应，我们将量化胶原酶mRNA表达的差异，在正常与患病的乳腺癌。 我们将研究是否与强力霉素，一种已知的抑制剂，基质金属蛋白酶的治疗，抑制MMP-1和MMP-13在AAA中的表达。 我们研究的长期目标是进一步表征AAA中的基质降解过程，并研究抑制基质破坏的方法。