Plasminogen activators in abdominal aortic aneurysmal disease.

Abstract

Abdominal aortic aneurysms (AAA) are characterized by the destruction of the extracellular matrix (ECM) of the aortic wall, particularly its elastin elements. The fibrinolytic system is known to mediate proteolysis within the ECM. Plasmin, which is generated by plasminogen activators (PA), is capable of destroying the ECM directly and indirectly via the activation of latent matrix metalloproteases (MMP). In addition, plasmin also synergistically enhances the ability of macrophages to destroy ECM. In AAA tissue, elevated levels of both urokinase-type and tissue-type plasminogen activators (u-PA and t-PA) have been documented. u-PA and t-PA have been localized to macrophages within the inflammatory infiltrate which is characteristic of AAA. mRNA expression of both type PAs is elevated as well in comparison to both normal and atherosclerotic occlusive aorta. Supporting the role of PAs in AAA pathogenesis is the fact that plasmin is elevated in AAA tissue, as are MMP. As with PA, MMP expression has been localized to macrophages. These data all suggest that the aortic wall is being degraded in AAA by a synergistic combination of macrophages, PA, and MMP.