TY - JOUR
T1 - Atorvastatin modulates matrix metalloproteinase expression, activity, and signaling in abdominal aortic aneurysms
AU - Schweitzer, Morris
AU - Mitmaker, Benjamin
AU - Obrand, Daniel
AU - Sheiner, Nathan
AU - Abraham, Cherrie
AU - Dostanic, Stevan
AU - Meilleur, Melissa
AU - Sugahara, Tomoko
AU - Chalifour, Lorraine E.
PY - 2010/2
Y1 - 2010/2
N2 - 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)-β (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-β signaling in the central region of human AAAs.
AB - 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)-β (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-β signaling in the central region of human AAAs.
KW - Abdominal aortic aneurysm
KW - Atorvastatin
KW - Matrix metalloproteinase
KW - TGF-β signaling
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U2 - 10.1177/1538574409348352
DO - 10.1177/1538574409348352
M3 - Article
C2 - 20034937
AN - SCOPUS:76049120774
SN - 1538-5744
VL - 44
SP - 116
EP - 122
JO - Vascular and Endovascular Surgery
JF - Vascular and Endovascular Surgery
IS - 2
ER -