Atorvastatin modulates matrix metalloproteinase expression, activity, and signaling in abdominal aortic aneurysms

Morris Schweitzer, Benjamin Mitmaker, Daniel Obrand, Nathan Sheiner, Cherrie Abraham, Stevan Dostanic, Melissa Meilleur, Tomoko Sugahara, Lorraine E. Chalifour

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)116-122
Number of pages7
JournalVascular and Endovascular Surgery
Volume44
Issue number2
DOIs
StatePublished - Feb 2010
Externally publishedYes

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Abdominal Aortic Aneurysm
Matrix Metalloproteinases
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Transforming Growth Factors
Tissue Inhibitor of Metalloproteinases
Matrix Metalloproteinase 1
Human Activities
Therapeutics
Mothers
Atorvastatin Calcium
Proteins

Keywords

  • Abdominal aortic aneurysm
  • Atorvastatin
  • Matrix metalloproteinase
  • TGF-β signaling

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Surgery

Cite this

Atorvastatin modulates matrix metalloproteinase expression, activity, and signaling in abdominal aortic aneurysms. / Schweitzer, Morris; Mitmaker, Benjamin; Obrand, Daniel; Sheiner, Nathan; Abraham, Cherrie; Dostanic, Stevan; Meilleur, Melissa; Sugahara, Tomoko; Chalifour, Lorraine E.

In: Vascular and Endovascular Surgery, Vol. 44, No. 2, 02.2010, p. 116-122.

Research output: Contribution to journalArticle

Schweitzer, M, Mitmaker, B, Obrand, D, Sheiner, N, Abraham, C, Dostanic, S, Meilleur, M, Sugahara, T & Chalifour, LE 2010, 'Atorvastatin modulates matrix metalloproteinase expression, activity, and signaling in abdominal aortic aneurysms', Vascular and Endovascular Surgery, vol. 44, no. 2, pp. 116-122. https://doi.org/10.1177/1538574409348352
Schweitzer, Morris ; Mitmaker, Benjamin ; Obrand, Daniel ; Sheiner, Nathan ; Abraham, Cherrie ; Dostanic, Stevan ; Meilleur, Melissa ; Sugahara, Tomoko ; Chalifour, Lorraine E. / Atorvastatin modulates matrix metalloproteinase expression, activity, and signaling in abdominal aortic aneurysms. In: Vascular and Endovascular Surgery. 2010 ; Vol. 44, No. 2. pp. 116-122.
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