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 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.
Schneiderman
J
J
Department of General and Vascular Surgery, Sheba Medical Center, Tel Hashomer, Israel.
Bordin
G M
GM
Adar
R
R
Smolinsky
A
A
Seiffert
D
D
Engelberg
I
I
Dilley
R B
RB
Thinnes
T
T
Loskutoff
D J
DJ
D000208:Acute Disease; D000784:Aortic Dissection / Q000378:metabolism* / Q000473:pathology; D017544:Aortic Aneurysm, Abdominal / Q000378:metabolism* / Q000473:pathology; D002908:Chronic Disease; D017364:Collagenases / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D020780:Matrix Metalloproteinase 9; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D010959:Tissue Plasminogen Activator / Q000235:genetics / Q000378:metabolism*; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics / Q000378:metabolism*
D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; C083866:T103N, KHRR 296-299 AAAA; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator; D017364:Collagenases; D020780:Matrix Metalloproteinase 9