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Expression of fibrinolytic genes in atherosclerotic abdominal aortic aneurysm wall. A possible mechanism for aneurysm expansion

Academic Article
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Overview

authors

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

publication date

  • July 1995

journal

  • Journal of Clinical Investigation  Journal

abstract

  • Expansion of atherosclerotic abdominal aortic aneurysm (AAA) has been attributed to remodeling of the extracellular matrix by active proteolysis. We used in situ hybridization to analyze the expression of fibrinolytic genes in aneurysm wall from eight AAA patients. All specimens exhibited specific areas of inflammatory infiltrates with macrophage-like cells expressing urokinase-type plasminogen activator (u-PA) and tissue-type PA (t-PA) mRNA. Type 1 PA inhibitor (PAI-1) mRNA was expressed at the base of the necrotic atheroma of all specimens and also within some of the inflammatory infiltrates where it frequently colocalized in regions containing u-PA and t-PA mRNA expressing cells. However, in these areas, the cellular distribution of the transcripts for t-PA and u-PA extended far beyond the areas of PAI-1 expression. These observations suggest a local ongoing proteolytic process, one which is only partially counteracted by the more restricted expression of PAI-1 mRNA. An abundance of capillaries was also obvious in all inflammatory infiltrates and may reflect local angiogenesis in response to active pericellular fibrinolysis. The increased fibrinolytic capacity in AAA wall may promote angiogenesis and contribute to local proteolytic degradation of the aortic wall leading to physical weakening and active expansion of the aneurysm.

subject areas

  • Adult
  • Aortic Aneurysm, Abdominal
  • Arteriosclerosis
  • Gene Expression
  • Humans
  • Plasminogen Activator Inhibitor 1
  • RNA, Messenger
  • Tissue Plasminogen Activator
  • Urokinase-Type Plasminogen Activator
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Research

keywords

  • ABDOMINAL AORTIC ANEURYSM
  • ANGIOGENESIS
  • IN SITU HYBRIDIZATION
  • PLASMINOGEN ACTIVATOR
  • PLASMINOGEN ACTIVATOR INHIBITOR
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Identity

PubMed Central ID

  • PMC185239

International Standard Serial Number (ISSN)

  • 0021-9738

Digital Object Identifier (DOI)

  • 10.1172/jci118079

PubMed ID

  • 7615837
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Additional Document Info

start page

  • 639

end page

  • 645

volume

  • 96

issue

  • 1

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