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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


Reference:

Erdozain, O. J., Pegrum, S., Winrow, V. R., Horrocks, M. and Stevens, C., 2011. 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. Journal of Vascular Research, 48 (2), pp. 163-170.

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Official URL:

http://dx.doi.org/10.1159/000318806

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

Details

Item Type Articles
CreatorsErdozain, O. J., Pegrum, S., Winrow, V. R., Horrocks, M. and Stevens, C.
DOI10.1159/000318806
Uncontrolled Keywordsets-1 transcription factor, abdominal aortic aneurysm, hypoxia, hypoxia-inducible factor-1 alpha, matrix metalloproteinase
DepartmentsFaculty of Humanities & Social Sciences > Health
RefereedNo
StatusPublished
ID Code21297

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