Histopathological analysis of cellular localization of cathepsins in abdominal aortic aneurysm wall

Abstract

An important feature of abdominal aortic aneurysm (AAA) is the destruction of vessel wall, especially elastin and collagen. Besides matrix metalloproteinases, cathepsins are the most potent elastolytic enzymes. The expression of cathepsins with known elastolytic and collagenolytic activities in the individual cells within AAA has not yet been determined. The vessel wall of 32 AAA patients and 10 organ donors was analysed by immunohistochemistry for expression of cathepsins B, D, K, L and S, and cystatin C in all cells localized within AAA. Luminal endothelial cells (ECs) of AAA were positive for cathepsin D and partially for cathepsins B, K and S. Endothelial cells of the neovessels and smooth muscle cells in the media were positive for all cathepsins tested, especially for cathepsin B. In the inflammatory infiltrate all cathepsins were expressed in the following pattern: B > D = S > K = L. Macrophages showed the highest staining intensity for all cathepsins. Furthermore, weak overall expression of cystatin C was observed in all the cells localized in the AAA with the exception of the ECs. There is markedly increased expression of the various cathepsins within the AAA wall compared to healthy aorta. Our data are broadly consistent with a role for cathepsins in AAA; and demonstrate expression of cathepsins D, B and S in phagocytic cells in the inflammatory infiltrate; and also may reveal a role for cathepsin B in lymphocytes.

Figure 1

Immunohistochemical staining of cathepsins and cystatin C in luminal endothelial cells and smooth muscle cells of the media within human healthy aorta.

Figure 2

Immunohistochemical staining of cathepsins and cystatin C in smooth muscle cells within human abdominal aortic aneurysm specimens.

Figure 3

Immunohistochemical staining of cathepsins and cystatin C in macrophages and macrophage-derived foam cells within human abdominal aortic aneurysm specimens.

Figure 4

Immunohistochemical staining of cathepsins and cystatin C in inflammatory cells within abdominal aortic aneurysm. The first column shows the cathepsin staining; the second, the staining of T lymphocytes (CD3); and the third, the staining of B lymphocytes (CD20).

Figure 5

Immunohistochemical staining of cathepsins and cystatin C in the immature neovessels (containing only endothelial cells without the stabilizing layer of smooth muscle cells) within abdominal aortic aneurysm specimens.

Figure 6

Immunohistochemical staining of cathepsins and cystatin C in the mature neovessels (containing both endothelial cells and smooth muscle cells) within abdominal aortic aneurysm specimens.