CELLULAR-LOCALIZATION OF MATRIX METALLOPROTEINASES IN THE ABDOMINAL AORTIC-ANEURYSM WALL

Purpose: This study explores the source(s) of the matrix-degrading proteinases, matrix metalloproteinase 1 (MMP-1; interstitial collagenase), matrix metalloproteinase 3 (MMP-3; stromelysin 1), and matrix metalloproteinase 9 (MMP-9; gelatinase B), previously implicated in abdominal aortic aneurysm (AAA) development. The possible involvement of the plasmin cascade in the activation of these proteinases was also explored by examining the presence of the urokinase-type plasminogen activator (uPA) in aneurysm wall. Methods: Immunohistochemical techniques were used to detect the presence of MMP-1, MMP-3 and MMP-9 proteins and uPA in fixed, paraffin-embedded tissue sections from AAA (n = 10) and control (n = 2) aortas. Results: The MMP-9 protein was localized to mononuclear cells in the AAA wall. Dual-labeling techniques confirmed the identity of these cells as macrophages. The MMP-3 protein and uPA were also detected primarily in the macrophage-like mononuclear cells infiltrating the aneurysmal aorta. Immunoreactive material to MMP-1 was demonstrated in mesenchymal cells ofthe AAA wall suggesting alternative expression and delivery of this enzyme in AAA. Conclusions: This work establishes the role of macrophages in the delivery, expression, and possible activation of matrix destructive proteinases during AAA pathogenesis and suggests a role for the activation of MMPs in the progression of the disease.