Possible key role for plasmin in the pathogenesis of abdominal aortic aneurysms.

BACKGROUND

Activation of proteolysis is characteristic of abdominal aortic aneurysm (AAA) disease, and by substrate gel enzymography with casein the most conspicuous proteinase of AAA wall has a molecular weight of approximately 80 kd. This activity has been resolved into separate metalloproteinase and serine proteinase (SP) components, by binding out the metalloproteinase by affinity to tissue inhibitor of metalloproteinases. Because plasmin plays a key role in activating members of the metalloproteinase family, the following experiments were done to test the hypothesis that the unknown SP is plasmin.

METHODS

Immunoblots, immunoprecipitations, and immunohistochemistry were performed by conventional methods with a specific polyclonal antibody to plasminogen.

RESULTS

Immunoblot analysis of extracts from AAA specimens (n = 7) revealed dense bands corresponding to known molecular forms of plasmin. Only trace amounts were detected in control aortic extracts (n = 4). When samples were equalized for total protein, the mean amount of immunoreactive material in the 80 kd band (in densitometric units) was 216 +/- 44 (SEM) for AAAs versus 27 +/- 15 (SEM) for controls (p < 0.01). The residual 80 kd SP activity on casein substrate gel enzymography was quenched by immunoprecipitation with the specific antibody. Immunohistochemistry revealed strong reactivity of the AAA wall.

CONCLUSIONS

Because plasmin plays a key role in the cascade for activation of the matrix metalloproteinase (including collagenase and the metalloelastases), the present results suggest that plasmin may be important in the sequence of events leading to the destruction of aortic matrix in AAA.