Effect of statins on proteolytic activity in the wall of abdominal aortic aneurysms.
BACKGROUND
The aim of this study was to examine the effect of statin treatment on the activity of proteases in the wall of abdominal aortic aneurysms (AAAs).


METHODS
The activities of matrix metalloproteinases (MMPs) 9 and 3, cathepsins B, H, K, L and S, and the cystatin C level were measured in extracts of AAA wall taken from 82 patients undergoing AAA repair; 21 patients were receiving statin treatment before surgery. All values were standardized against soluble protein (SP) concentration in the extract, and reported as median (interquartile range) or mean(s.e.m.).


RESULTS
The two groups had similar demographics. Reduced activity of MMP-9 (43 (34-56) versus 80 (62-110) pg per mg SP; P < 0.001), cathepsin H (183 (117-366) versus 321 (172-644) nmol 4-methylcoumarin-7-amide released per mg SP; P = 0.016) and cathepsin L (102 (51-372) versus 287 (112-816) micromol 7-amino-4-trifluoromethylcoumarin released per mg SP; P = 0.020) was found in the statin-treated aortas compared with AAAs from patients not taking a statin. The statin-treated group had lower MMP-3 activity, but this did not reach statistical significance (P = 0.053). Cystatin C levels were higher in statin-treated aortas than in controls (41.3(3.1) versus 28.9(2.1) ng per mg SP; P = 0.003).


CONCLUSIONS
Statins decreased the activity of proteases that have been implicated in aneurysm disease.
Abisi
S
S
Academic Department of Surgery, Cardiovascular Division, King's College School of Medicine, London, UK.
Burnand
K G
KG
Humphries
J
J
Waltham
M
M
Taylor
P
P
Smith
A
A
D000368:Aged; D001012:Aorta, Abdominal / Q000201:enzymology*; D017544:Aortic Aneurysm, Abdominal / Q000201:enzymology*; D002403:Cathepsins / Q000378:metabolism; D055316:Cystatin C; D015891:Cystatins / Q000378:metabolism; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*
C525030:CST3 protein, human; D055316:Cystatin C; D015891:Cystatins; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D002403:Cathepsins; D019278:Matrix Metalloproteinase 3; D020780:Matrix Metalloproteinase 9