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
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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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
|Creators||Erdozain, O. J., Pegrum, S., Winrow, V. R., Horrocks, M. and Stevens, C.|
|Uncontrolled Keywords||ets-1 transcription factor, abdominal aortic aneurysm, hypoxia, hypoxia-inducible factor-1 alpha, matrix metalloproteinase|
|Departments||Faculty of Humanities & Social Sciences > Health|
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