Matrix metalloproteinase 8 (neutrophil collagenase) in the pathogenesis of abdominal aortic aneurysm.
BACKGROUND
Loss of elastin is the initiating event in abdominal aortic aneurysm (AAA) formation, whereas loss of collagen is required for continued expansion. The elastolytic matrix metalloproteinases (MMPs) 2 and 9 are well described, but the source of excessive collagenolysis remains undefined. The aim of this study was to determine the expression of MMP-8, a potent type I collagenase, in normal aorta and AAA.


METHODS
Infrarenal aortic biopsies were taken from 40 AAA and ten age-matched normal aortas. The concentrations of MMP-8 protein and its inhibitors, tissue inhibitor of metalloproteinase (TIMP) 1 and TIMP-2, were quantified by enzyme-linked immunosorbent assay. Immunohistochemistry was used to localize MMP-8 expression.


RESULTS
MMP-8 concentrations were significantly raised in AAA compared with normal aorta (active MMP-8: 4.5 versus 0.5 ng per mg protein, P < 0.001; total MMP-8: 16.6 versus 2.8 ng per mg protein, P < 0.001). Levels of TIMP-1 and TIMP-2 were significantly lower in AAA than in normal aortic samples (TIMP-1: 142.2 versus 302.8 ng per mg protein; P = 0.010; TIMP-2: 9.2 versus 33.1 ng per mg protein, P < 0.001). Immunohistochemistry localized MMP-8 to mesenchymal cells within the adventitia of the aortic wall.


CONCLUSIONS
The high concentration of MMP-8 in aortic aneurysms represents a potent pathway for collagen degradation, and hence aneurysm formation and expansion.
Wilson
W R W
WR
Department of Vascular Surgery, St George's Hospital Medical School, London, UK.
Schwalbe
E C
EC
Jones
J L
JL
Bell
P R F
PR
Thompson
M M
MM
D000368:Aged; D001012:Aorta, Abdominal / Q000378:metabolism*; D017544:Aortic Aneurysm, Abdominal / Q000201:enzymology* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D020784:Matrix Metalloproteinase 8 / Q000378:metabolism*; D008875:Middle Aged; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism
D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D020784:Matrix Metalloproteinase 8