Atorvastatin modulates matrix metalloproteinase expression, activity, and signaling in abdominal aortic aneurysms.
Statins may reduce abdominal aortic aneurysm (AAA) progression. We sought to measure how atorvastatin (AT) treatment might modulate matrix metalloproteinase (MMP) expression and/or activity in human AAA. Tissue from human AAAs at surgical repair was obtained from patients who were either not on statins (NST, n = 19) or treated with AT (n = 19). Immunoblots measured expression and zymography measured activity. Expression of most proteins was greater in the central compared with distal AAA region. Matrix metalloproteinase 1, MMP2, MMP3, MMP9, Tissue Inhibitor of Metalloproteinase (TIMP2), TIMP3, TIMP4, or total Sma Mothers Against Decapentaplegia (SMAD2) expression did not differ with treatment. There was a trend toward reduced MMP8 and TIMP1 expression and MMP2 zymographic activity in the AT-treatment group. In contrast, AT-treated samples had significantly reduced MMP13 (P = .02), latent-transforming growth factor (TGF)-beta (P = .02), and phospho-SMAD2 (P = .029) expression than NST-treated samples. We conclude that the AT-mediated decrease in MMP expression and activity reduces TGF-beta signaling in the central region of human AAAs.
Schweitzer
Morris
M
Department of Endocrinology, Sir Mortimer B. Davis-Jewish General Hospital, Montreal, Quebec, Canada. morris.schweitzer@mcgill.ca
Mitmaker
Benjamin
B
Obrand
Daniel
D
Sheiner
Nathan
N
Abraham
Cherrie
C
Dostanic
Stevan
S
Meilleur
Melissa
M
Sugahara
Tomoko
T
Chalifour
Lorraine E
LE
D000368:Aged; D001012:Aorta, Abdominal / Q000187:drug effects* / Q000201:enzymology / Q000601:surgery; D017544:Aortic Aneurysm, Abdominal / Q000188:drug therapy* / Q000201:enzymology / Q000601:surgery; D000069059:Atorvastatin; D015536:Down-Regulation; D005260:Female; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D010766:Phosphorylation; D011758:Pyrroles / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects*; D051899:Smad2 Protein / Q000378:metabolism; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D051899:Smad2 Protein; D019714:Tissue Inhibitor of Metalloproteinases; D016212:Transforming Growth Factor beta; D000069059:Atorvastatin; D020782:Matrix Metalloproteinases