Stromelysin-1 (matrix metalloproteinase-3) and tissue inhibitor of metalloproteinase-3 are overexpressed in the wall of abdominal aortic aneurysms.
BACKGROUND
Atherosclerosis is implicated in the pathogenesis of abdominal aortic aneurysm (AAA) but more often causes aortic occlusive disease (AOD). The matrix metalloproteinases (MMPs) degrade extracellular matrix and may play a central role in the pathogenesis of AAA. The aim of this study was to examine differences in the patterns of MMP and MMP inhibitor expression between AAA and AOD.


RESULTS
The expression of mRNA for 14 MMPs and 4 tissue inhibitors of metalloproteinases (TIMPs) was estimated in samples of aortic wall from 8 patients with AAA and 8 with AOD using the reverse-transcriptase polymerase chain reaction with a synthetic multicompetitor standard. AAA wall expressed significantly more stromelysin-1 (MMP-3) (mean log(10) ratio [copy enzyme cDNA/copy GAPDH cDNA], -1.9; range, -3.3 to -0.7) than the AOD wall (mean, 4; range, -5.7 to -2.4), P<0.005. TIMP-3 expression was significantly higher in AAA (mean, -1.7; range, -2.9 to -1.0) than AOD (mean, -3.6; range, -5.7 to -1.8), P<0.01. Expression of 8 other MMPs (1, 2, 7, 9, 11, 12, 14, and 17) was detected and was similar in AAA and AOD. Expression of the remaining 5 MMPs (-8, -10, -13, -15, and -16) was not detected in any of the samples.


CONCLUSIONS
Both AAA and AOD walls express similar levels of a wide range of MMPs, including cell membrane-bound MT-MMPs. Stromelysin-1 (MMP-3) and TIMP-3 were, however, over expressed in the AAA samples and may be involved aneurysm pathogenesis. Stromelysin-1 could provide a target for pharmacological inhibition.
Carrell
Tom W G
TW
Academic Department of Surgery, Kings College, London, UK.
Burnand
Kevin G
KG
Wells
Graham M A
GM
Clements
John M
JM
Smith
Alberto
A
D000009:Abdominal Muscles / Q000201:enzymology*; D000368:Aged; D017544:Aortic Aneurysm, Abdominal / Q000201:enzymology* / Q000235:genetics; D001018:Aortic Diseases / Q000201:enzymology / Q000235:genetics; D001157:Arterial Occlusive Diseases / Q000201:enzymology / Q000235:genetics; D001161:Arteriosclerosis / Q000201:enzymology / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000096:biosynthesis* / Q000235:genetics; D020782:Matrix Metalloproteinases / Q000096:biosynthesis / Q000235:genetics; D008875:Middle Aged; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000096:biosynthesis* / Q000235:genetics; D019714:Tissue Inhibitor of Metalloproteinases / Q000096:biosynthesis / Q000235:genetics; D015533:Transcriptional Activation
D012333:RNA, Messenger; D019717:Tissue Inhibitor of Metalloproteinase-3; D019714:Tissue Inhibitor of Metalloproteinases; D020782:Matrix Metalloproteinases; D019278:Matrix Metalloproteinase 3