TY - JOUR
T1 - 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
AU - Erdozain, O J
AU - Pegrum, Susan
AU - Winrow, V R
AU - Horrocks, Michael
AU - Stevens, Clifford
PY - 2011
Y1 - 2011
N2 - 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
AB - 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
KW - Ets-1 transcription factor
KW - abdominal aortic aneurysm
KW - hypoxia
KW - hypoxia-inducible factor-1 alpha
KW - matrix metalloproteinase
UR - http://www.scopus.com/inward/record.url?scp=77957748627&partnerID=8YFLogxK
UR - http://dx.doi.org/10.1159/000318806
U2 - 10.1159/000318806
DO - 10.1159/000318806
M3 - Article
SN - 1018-1172
VL - 48
SP - 163
EP - 170
JO - Journal of Vascular Research
JF - Journal of Vascular Research
IS - 2
ER -