TY - JOUR
T1 - Matrix metalloproteinase-8 and -9 are increased at the site of abdominal aortic aneurysm rupture
AU - Wilson, Richard W.
AU - Anderton, Marcus
AU - Schwalbe, Edward C.
AU - Jones, J. Louise
AU - Furness, Peter N.
AU - Bell, Peter R.F.
AU - Thompson, Matthew M.
PY - 2006/1/24
Y1 - 2006/1/24
N2 - BACKGROUND-: Abdominal aortic aneurysm (AAA) expansion is characterized by extracellular matrix degradation and widespread inflammation. In contrast, the processes that characterize AAA rupture are not well understood. The aim of this study was to investigate the proteolytic and cellular activity of ruptured AAA, focusing on matrix metalloproteinases (MMPs) and their inhibitors (TIMPs). METHODS AND RESULTS-: Anterior aneurysm wall biopsies were taken from 55 nonruptured and 21 ruptured AAAs. A further biopsy from the site of rupture was taken from 12 of the ruptured AAAs. MMP-1, -2, -3, -8, -9, and -13, as well as TIMP-1 and -2, were quantified in each biopsy with ELISA. A comparison of anterior aneurysm biopsies showed no difference in MMP or TIMP concentrations between nonruptured and ruptured AAA. In a comparison of ruptured AAA biopsies, MMP-8 and -9 levels were significantly elevated in the 12 rupture site biopsies compared with their 12 paired anterior wall biopsies, whereas other MMPs and TIMPs showed no difference (MMP-8, P<0.001; MMP-9, P=0.01). MMP-8 and -9 expression was mediated by native mesenchymal cells and was independent of the inflammatory infiltrate. CONCLUSIONS-: A localized increase in MMP-8 and -9, mediated by native mesenchymal cells, presents a potential pathway for collagen breakdown and AAA rupture.
AB - BACKGROUND-: Abdominal aortic aneurysm (AAA) expansion is characterized by extracellular matrix degradation and widespread inflammation. In contrast, the processes that characterize AAA rupture are not well understood. The aim of this study was to investigate the proteolytic and cellular activity of ruptured AAA, focusing on matrix metalloproteinases (MMPs) and their inhibitors (TIMPs). METHODS AND RESULTS-: Anterior aneurysm wall biopsies were taken from 55 nonruptured and 21 ruptured AAAs. A further biopsy from the site of rupture was taken from 12 of the ruptured AAAs. MMP-1, -2, -3, -8, -9, and -13, as well as TIMP-1 and -2, were quantified in each biopsy with ELISA. A comparison of anterior aneurysm biopsies showed no difference in MMP or TIMP concentrations between nonruptured and ruptured AAA. In a comparison of ruptured AAA biopsies, MMP-8 and -9 levels were significantly elevated in the 12 rupture site biopsies compared with their 12 paired anterior wall biopsies, whereas other MMPs and TIMPs showed no difference (MMP-8, P<0.001; MMP-9, P=0.01). MMP-8 and -9 expression was mediated by native mesenchymal cells and was independent of the inflammatory infiltrate. CONCLUSIONS-: A localized increase in MMP-8 and -9, mediated by native mesenchymal cells, presents a potential pathway for collagen breakdown and AAA rupture.
KW - Aneurysm
KW - Inflammation
KW - Metalloproteinases
KW - Rupture
UR - http://www.scopus.com/inward/record.url?scp=33644858502&partnerID=8YFLogxK
U2 - 10.1161/CIRCULATIONAHA.105.551572
DO - 10.1161/CIRCULATIONAHA.105.551572
M3 - Article
C2 - 16432074
AN - SCOPUS:33644858502
SN - 0009-7322
VL - 113
SP - 438
EP - 445
JO - Circulation
JF - Circulation
IS - 3
ER -