PATTERNS OF EXPRESSION OF FIBRINOLYTIC GENES AND MATRIX METALLOPROTEINASE-9 IN DISSECTING AORTIC-ANEURYSMS

Although extensive tissue remodeling occurs during the various phases of aortic dissection, the underlying proteinases remain to be identifi ed. Matrix metalloproteinase-9 (MMP-9) and components of the fibrinoly tic system have been implicated in numerous tissue remodeling events a nd were therefore analyzed in surgical specimens of acute (n = 9), sub acute (n = 4), and chronic (n = 7) aortic dissection by in situ hybrid ization. In the acute phase, intense plasminogen activator inhibitor 1 (PAI-1) gene expression was apparent in areas interfacing the dissect ing hematoma, but no tissue-type PA (t-PA), urokinase-type PA (u-PA), or MMP-9 mRNAs were detected. Although PAI-1 mRNA was still present in the subacute phase, t-PA, u-PA, and MMP-9 mRNAs were now obvious, wit h PA gene expression co-localizing with areas of PAI-1 gene expression . In the chronic phase, PAI-1 mRNA was demonstrated around erythrocyte extravasations and surrounding bands of medial degeneration. However, there was little expression of PAs in these areas, and no MMP-9 was d etected. Thus, fubrinolytic genes and MMP-9 are differentially express ed during the progression of aortic dissections. The kinetics of expre ssion are consistent with acute fibrinolytic shutdown in response to t he initial injury, a secondary subacute phase with active proteolysis, and finally, a chronic hypofibrinolytic state. Extensive neovasculari zation in the chronic phase may further reduce the physical stability of the dissected wall.