Matrix metalloproteinase-2 production and its binding to the matrix are increased in abdominal aortic aneurysms

Valerie Davis, Raisa Persidskaia, Lisa Baca-Regen, Yoshifumi Itoh, Hideaki Nagase, Yuri Persidsky, Anuja Ghorpade, B. Timothy Baxter

Research output: Contribution to journalArticle

212 Scopus citations

Abstract

Degradation of the elastic media is a hallmark of abdominal aortic aneurysms (AAAs). We examined the expression of 2 elastolytic matrix metalloproteinases (MMPs), MMP-2 and MMP-9, in AAA aortic tissues compared with those from atherosclerotic occlusive disease (AOD) and nondiseased control tissues. Quantitative competitive reverse transcription-polymerase chain reaction and gelatin zymography showed increased MMP-9 mRNA and protein in both AAA and AOD tissues compared with those in control tissue, but there was no significant difference between AAA and AOD. In contrast, MMP-2 mRNA and protein levels were significantly higher in AAA than in AOD or control tissues. Sequential extraction of the MMPs from the aortic tissue with a physiological salt solution, 2% dimethylsulfoxide (DMSO), and 10 mol/L urea showed that large amounts of MMP-2 and MMP-9 were bound to the matrix. The most conspicuous finding was that the levels of MMP-2 were significantly elevated in the DMSO fraction in AAA tissues compared with AOD and control tissues. In addition, a large portion of MMP-2 found in the DMSO and urea fractions was in the active 62-kDa form, indicating that the precursor of MMP-2 in AAA is largely activated locally and binds to the tissue matrix tightly. By immunolocalization, MMP-9 was found to be primarily produced by macrophages and MMP-2 by mesenchymal cells. The production of MMP-2 was prominent when mesenchymal cells were surrounded by inflammatory cells, suggesting paracrine modulation of MMP-2 expression in AAAs. These observations emphasize that MMP-2 participates in the progression of AAAs by degrading aortic tissue matrix components.

Original languageEnglish (US)
Pages (from-to)1625-1633
Number of pages9
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume18
Issue number10
DOIs
StatePublished - Jan 1 1998

Keywords

  • Abdominal aortic aneurysms
  • Lymphocytes
  • Macrophages
  • Matrix metalloproteinases
  • Smooth muscle cells

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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