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

Academic Article
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Overview

authors

  • Schneiderman, J.
  • Bordin, G. M.
  • Adar, R.
  • Smolinsky, A.
  • Seiffert, D.
  • Engelberg, I.
  • Dilley, R. B.
  • Thinnes, T.
  • Loskutoff, David J.

publication date

  • March 1998

journal

  • American Journal of Pathology  Journal

abstract

  • 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.

subject areas

  • Acute Disease
  • Aneurysm, Dissecting
  • Aortic Aneurysm, Abdominal
  • Chronic Disease
  • Collagenases
  • Gene Expression
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization
  • Matrix Metalloproteinase 9
  • Plasminogen Activator Inhibitor 1
  • RNA, Messenger
  • Tissue Plasminogen Activator
  • Urokinase-Type Plasminogen Activator
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Identity

PubMed Central ID

  • PMC1858402

International Standard Serial Number (ISSN)

  • 0002-9440

PubMed ID

  • 9502412
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Additional Document Info

start page

  • 703

end page

  • 710

volume

  • 152

issue

  • 3

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