Patterns of expression of fibrinolytic genes and matrix metalloproteinase-9 in dissecting aortic aneurysms

• Published in: The American journal of pathology Vol. 152; no. 3; pp. 703 - 710
• Main Authors: Schneiderman, J, Bordin, GM, Adar, R, Smolinsky, A, Seiffert, D, Engelberg, I, Dilley, RB, Thinnes, T, Loskutoff, DJ
• Format: Journal Article
• Language: English
• Published: Bethesda, MD ASIP 01.03.1998; American Society for Investigative Pathology
• Subjects: Acute Disease; Aneurysm, Dissecting - metabolism; Aneurysm, Dissecting - pathology; Aortic Aneurysm, Abdominal - metabolism; Aortic Aneurysm, Abdominal - pathology; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Chronic Disease; Collagenases - genetics; Collagenases - metabolism; Diseases of the aorta; Gene Expression; Humans; Immunohistochemistry; In Situ Hybridization; Matrix Metalloproteinase 9; Medical sciences; Plasminogen Activator Inhibitor 1 - genetics; Plasminogen Activator Inhibitor 1 - metabolism; RNA, Messenger - metabolism; Tissue Plasminogen Activator - genetics; Tissue Plasminogen Activator - metabolism; Urokinase-Type Plasminogen Activator - genetics; Urokinase-Type Plasminogen Activator - metabolism; Human; Immunohistochemistry; Enzyme; Pathogenesis; In situ; Cardiovascular disease; Metalloendopeptidases; Hybridization; Gene expression; Fibrinolysis; Gelatinase B; Vascular disease; Dissecting aneurysm; Pathology; Peptidases; Hydrolases; Aorta; Kinetics; Molecular biology; Aortic disease
• ISSN: 0002-9440; 1525-2191

Although extensive tissue remodeling occurs during the various phases of aortic dissection, the underlying proteinases remain to be identified. Matrix metalloproteinase-9 (MMP-9) and components of the fibrinolytic system have been implicated in numerous tissue remodeling events and were therefore analyzed in surgical specimens of acute (n = 9), subacute (n = 4), and chronic (n = 7) aortic dissection by in situ hybridization. In the acute phase, intense plasminogen activator inhibitor 1 (PAI-1) gene expression was apparent in areas interfacing the dissecting 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, with 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 detected. Thus, fibrinolytic genes and MMP-9 are differentially expressed during the progression of aortic dissections. The kinetics of expression are consistent with acute fibrinolytic shutdown in response to the initial injury, a secondary subacute phase with active proteolysis, and finally, a chronic hypofibrinolytic state. Extensive neovascularization in the chronic phase may further reduce the physical stability of the dissected wall.