The expression and localization of membrane type-1 matrix metalloproteinase in human abdominal aortic aneurysms

Background and Objective: Matrix metalloproteinase-2 (MMP-2) degrades both fibrillar collagens and elastin, MMP-2 is secreted as a latent 72-kd proenz yme that must be proteolytically processed to the 62-kd active form. In our laboratory we demonstrated a significant increase of active, matrix-bound MMP-2 in abdominal aortic aneurysmal (AAA) tissue compared with nonaneurysm al aorta with arteriosclerotic occlusive disease and normal aortic tissue. This increase in active MMP-2 is considered to be important in aneurysm pat hogenesis, but the mechanism of its activation in aortic tissue is unknown. Membrane type-1 MMP (MT-1 MMP) is known to be an activator of MMP-2. The p urpose of this study was to determine MT-1 MMP expression and its involveme nt in pro-MMP-2 activation in human aneurysmal tissue. Methods: Infrarenal aortic tissue was obtained during the surgical repair o f AAAs or the bypass of aortoiliac occlusive disease, or from nondiseased a orta, and the expression of MT-1 MMP messenger RNA was determined with Nort hern blot analysis. MT-1 MMP protein was determined with immunoblot and imm unohistochemistry. The ability of aortic tissue to activate pro-MMP-2 was a nalyzed by incubating aortic tissue with exogenous radiolabeled pro-MMP-2. Results: MT-1 MMP messenger RNA and protein are increased in AAA (P <.05) c ompared with arteriosclerotic occlusive disease and normal aortic tissue. I mmunohistochemical analysis localized MT-1 MMP to aortic smooth muscle cell s and macrophages in aneurysmal tissue. AAA tissue demonstrated a greater c apacity to activate exogenous pro-MMP-2 compared with atherosclerotic and n ormal aortic tissue (P <.05). Conclusion: These studies demonstrate that MT-1 MMP is increased in AAA tis sue and suggest that it may be important in AAA pathogenesis through its ab ility to activate pro-MMP-2.