Treatment with simvastatin suppresses the development of experimental abdominal aortic aneurysms in normal and hypercholesterolemic mice

Eric F. Steinmetz, Celine Buckley, Murray L. Shames, Terri L. Ennis, Sarah J. Vanvickle-Chavez, Dongli Mao, Lee A. Goeddel, Cherady J. Hawkins, Robert W. Thompson

Research output: Contribution to journalArticle

Abstract

Objective: To determine if treatment with hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) can influence the development of experimental abdominal aortic aneurysms (AAAs). Summary Background Data: AAAs are associated with atherosclerosis, chronic inflammation, and matrix metalloproteinase (MMP)-mediated connective tissue destruction. Because statins exert antiinflammatory activities independent of their lipid-lowering effects, these agents may help suppress aneurysmal degeneration. Methods: C57B1/6 wild-type and hypercholesterolemic apoE-deficient mice underwent transient perfusion of the aorta with elastase followed by subcutaneous treatment with either 2 mg/kg simvastatin per day or vehicle. Aortic diameter (AD) was measured before and 14 days after elastase perfusion. The extent of aortic dilatation (ΔAD) was determined with AAAs defined as ΔAD >100%. Results: Wild-type mice treated with simvastatin exhibited a 21% reduction in ΔAD and a 33% reduction in AAAs compared with vehicle-treated controls. Suppression of AAAs in simvastatin-treated mice was associated with preservation of medial elastin and vascular smooth muscle cells, as well as a relative reduction in aortic wall expression of MMP-9 and a relative increase in expression of TIMP-1. In hypercholesterolemic apoE-deficient mice, treatment with simvastatin was associated with a 26% reduction in ΔAD and a 30% reduction in AAAs. Treatment with simvastatin had no effect on serum cholesterol levels in either normal or hypercholesterolemic mice. Conclusions: Treatment with simvastatin suppresses the development of experimental AAAs in both normal and hypercholesterolemic mice. The mechanisms of this effect are independent of lipid-lowering and include preservation of medial elastin and smooth muscle cells, as well as altered aortic wall expression of MMPs and their inhibitors.

Original languageEnglish (US)
Pages (from-to)92-101
Number of pages10
JournalAnnals of surgery
Volume241
Issue number1
DOIs
StatePublished - Jan 1 2005
Externally publishedYes

ASJC Scopus subject areas

  • Surgery

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    Steinmetz, E. F., Buckley, C., Shames, M. L., Ennis, T. L., Vanvickle-Chavez, S. J., Mao, D., Goeddel, L. A., Hawkins, C. J., & Thompson, R. W. (2005). Treatment with simvastatin suppresses the development of experimental abdominal aortic aneurysms in normal and hypercholesterolemic mice. Annals of surgery, 241(1), 92-101. https://doi.org/10.1097/01.sla.0000150258.36236.e0