Localization of matrix metalloproteinase 2 within the aneurysmal and normal aortic wall

Background: Current research has shed new light on the role of matrix metal loproteinase (MMP) 2 in the development of abdominal aortic aneurysms (AAAs ). MMP-2 is a major protease in the wall of small aneurysms and is produced at increased levels by smooth muscle cells derived from AAAs compared with normal controls. In vivo, MMP-2 is produced as an inactive proenzyme that is activated predominantly by the cell membrane-bound enzyme, membrane type 1 matrix metalloproteinase (MT1-MMP). This study investigated the producti on of the MMP-2-MT1-MMP-tissue inhibitor of metalloproteinases (TIMP) 2 sys tem within the wall of aortic aneurysms and in age-matched control arterial tissue. Methods: Arterial tissue from four patients with aortic aneurysms and four age-matched aortic samples was examined for the production and expression o f MMP-2, TIMP-2 and MT1-MMP protein using immunohistochemistry, in situ hyb ridization and in situ zymography. Results: All components of the MMP-2-TIMP-2-MT1-MMP enzyme system were dete cted in the arterial wall of both aneurysm and control samples, specificall y in the medial tissue. The enzymes colocalized with medial smooth muscle c ells. Gelatinolyde activity was localized to elastin fibres in normal and a neurysmal aorta. Conclusion: The presence of MT1-MMP within the media of arterial tissue sug gests a powerful pathway for the activation of MMP-2. The localization of t he MMP-2-TIMP-2-MT1-MMP enzyme system to the medial layer of the arterial w all gives support to the concept that this system may play an aetiological role in the pathogenesis of AAAs.