Decreased tissue inhibitor of metalloproteinases (TIMP) in abdominal aortic aneurysm tissue: a preliminary report

Abstract

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.