Treatment with simvastatin inhibits the formation of abdominal aortic aneurysms in rabbits

Ann Vasc Surg. 2012 Feb;26(2):250-8. doi: 10.1016/j.avsg.2011.09.003. Epub 2012 Jan 4.


Background: Abdominal aortic aneurysm (AAA) is a common and lethal disease. AAAs are associated with atherosclerosis, chronic inflammation, and extracellular matrix degradation. The aim of this study was to determine whether treatment with simvastatin can influence the development of experimental aortic aneurysms in a rabbit model.

Materials and methods: A total of 76 rabbits were randomized in four groups: in group I (n = 12), where the abdominal aortas were exposed to 0.9% NaCl, and in group II (n = 24), group III (n = 24) and group IV (n = 18), where the aortas were exposed to CaCl2 0.5 mol/L for 15 minutes after laparotomy. Group III received 2 mg/kg simvastatin daily starting 7 days before laparotomy, and in group IV, the daily treatment with simvastatin started 7 days after laparotomy. Animals were sacrificed at intervals of first, second, third, and fourth week to obtain measurements of aortic diameter and histological examination. Moreover, immunohistochemistry was used in order to examine the relative distribution of matrix metalloproteinases (MMPs) 2 and 9 (MMP-2 and MMP-9, respectively) and tissue inhibitor 1 of MMPs within the aortic aneurysms.

Results: The increase of aortic diameter in animals of group I ranged from 4.6% to 7.6%; in group II, from 41% to 85% (P < 0.001 vs. group I); in group III, from 9% to 18% (group II vs. group III, P < 0.001); and in group IV; from 36% to 38%. Moreover, aortic specimens of group II presented a statistically significant increase in MMP-2 and MMP-9 immunoexpression compared with other groups (I, III, IV) (P < 0.05 for all comparisons), with the exception of animals of group IV at the end of second week. Immunoreactivity of tissue inhibitor 1 of MMPs was not statistically different among groups II, III, and IV.

Conclusions: Simvastatin may prove clinically significant in suppressing the development and expansion of AAAs and, thereby, in reducing the risk of rupture and the need for repair.

MeSH terms

  • Animals
  • Aorta, Abdominal / drug effects*
  • Aorta, Abdominal / metabolism
  • Aorta, Abdominal / pathology
  • Aortic Aneurysm, Abdominal / chemically induced
  • Aortic Aneurysm, Abdominal / metabolism
  • Aortic Aneurysm, Abdominal / pathology
  • Aortic Aneurysm, Abdominal / prevention & control*
  • Calcium Chloride
  • Disease Models, Animal
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
  • Immunohistochemistry
  • Male
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Rabbits
  • Simvastatin / pharmacology*
  • Time Factors
  • Tissue Inhibitor of Metalloproteinase-1 / metabolism


  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Tissue Inhibitor of Metalloproteinase-1
  • Simvastatin
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9
  • Calcium Chloride