Brophy C M, Marks W H, Reilly J M, Tilson M D
Department of Surgery, New England Deaconess Hospital, Boston, Massachusetts.
J Surg Res. 1991 Jun;50(6):653-7. doi: 10.1016/0022-4804(91)90058-t.
Important concepts underlying the pathophysiology of abdominal aortic aneurysm (AAA) disease include a genetic predisposition, male predominance, and increased proteolysis. Proteolytic activity is carefully controlled by an abundance of protease inhibitors and the increased proteolysis may reflect a decrease in inhibitory activity. The recent assignment for the major tissue inhibitor of metalloproteinases (TIMP) to the X chromosome provides a potential link between the male predominance and increased proteolysis noted in AAA. The purpose of this investigation was to measure the amount of TIMP in normal and diseased aorta. A polyclonal antibody to recombinant human TIMP was produced in rabbit and used to establish an immunoassay. Immunoreactive TIMP in normal and diseased aorta was then measured. There was more TIMP in the matrix-associated fraction than in the soluble fraction. There was significantly less immunoreactive TIMP in aortic extracts from AAA than from control as measured both by Western blot and radioimmunoassay. These results suggest that a diminished amount of TIMP in the aortic matrix in AAA patients may contribute to the increased proteolysis observed in AAA.
腹主动脉瘤（AAA）疾病病理生理学的重要潜在概念包括遗传易感性、男性居多以及蛋白水解增加。蛋白水解活性受到大量蛋白酶抑制剂的严格控制，蛋白水解增加可能反映了抑制活性的降低。金属蛋白酶组织抑制剂（TIMP）最近被定位到X染色体，这为AAA中男性居多和蛋白水解增加之间提供了潜在联系。本研究的目的是测量正常和病变主动脉中TIMP的含量。用重组人TIMP在兔体内制备了多克隆抗体，并用于建立免疫测定法。然后测量正常和病变主动脉中的免疫反应性TIMP。与可溶性部分相比，基质相关部分的TIMP更多。通过蛋白质印迹法和放射免疫测定法测量，AAA主动脉提取物中的免疫反应性TIMP明显少于对照。这些结果表明，AAA患者主动脉基质中TIMP含量减少可能导致AAA中观察到的蛋白水解增加。
