Hypoxia in abdominal aortic aneurysm supports a role for HIF-1 alpha and Ets-1 as drivers of matrix metalloproteinase upregulation in human aortic smooth muscle cells

O J Erdozain, Susan Pegrum, V R Winrow, Michael Horrocks, Clifford Stevens

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Background/Aims: We sought to determine whether hypoxia is an initiating factor in the matrix metalloproteinase-2 (MMP-2) up-regulation observed in abdominal aortic aneurysm (AAA) and whether hypoxia-inducible factor-1 alpha (HIF-1 alpha) or Ets-1 are mediating factors.

Methods: Human AAA and normal aorta were analysed for MMP-2, HIF-1 alpha and Ets-1 by immunohistochemistry. Human aortic smooth muscle cell (HASMC) cultures exposed to experimental hypoxia were analysed for hypoxia-induced proteins using gelatin zymography and immunoblotting. Multiplex PCR was used to detect MMP-1, membrane-type (MT)-MMP-1, MMP-2, MMP-3, MMP-7 and MMP-9.

Results: AAA tissues expressed HIF-1 alpha , MMP-2 and Ets-1 strongly within smooth muscle cells and inflammatory infiltrate of the tunica media. Up-regulated MMP-2 was detected in hypoxia-exposed HASMC (p<0.05), with MMP-9 elevations after exposure to sequential O-2 decreases (p<0.05). Immunoblotting confirmed HIF-1 alpha, Ets-1, VEGF and MMP-2 are up-regulated in HASMC exposed to hypoxia (p<0.05), while transcription for MMP-1, MT-MMP-1

Original languageEnglish
Pages (from-to)163-170
Number of pages8
JournalJournal of Vascular Research
Volume48
Issue number2
DOIs
Publication statusPublished - 2011

Keywords

  • Ets-1 transcription factor
  • abdominal aortic aneurysm
  • hypoxia
  • hypoxia-inducible factor-1 alpha
  • matrix metalloproteinase

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