Efficacy of Simvastatin in Reducing Aortic Dilatation in Mouse Models of Abdominal Aortic Aneurysm
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Currently there is no effective drug therapy for abdominal aortic aneurysm (AAA). The aim of this study was to assess the ability of simvastatin to inhibit aortic dilatation in two mouse models.
AAAs were induced in two mice strains predisposed to atherosclerosis. Firstly, 11 weeks old male apolipoprotein E deficient (ApoE−/−) mice were given vehicle control (n = 27) or simvastatin (50 mg/kg/d, n = 27) prior to being infused with angiotensin II (1 μg/kg/min) subcutaneously for 4 weeks. Secondly, 9 weeks old male low-density lipoprotein receptor deficient (LDLR−/−) mice were fed a high fat diet, then given vehicle control (n = 17) or simvastatin (50 mg/kg/d, n = 18) and from 14 to 18 weeks of age infused with angiotensin II. Subsequently aortas were harvested, maximum suprarenal aortic diameter measured, aortic arch atheroma assessed by sudan IV staining and blood extracted to measure serum lipids. In the LDLR−/− mice the suprarenal aortic diameter was also measured by ultrasound prior to aortic harvesting.
In ApoE−/− mice suprarenal aortic diameters were modestly smaller in animals receiving simvastatin without significant change despite reduction in macrophage infiltration. Aortic arch atheroma was substantially reduced in LDLR−/− mice receiving simvastatin with borderline significant reduction in suprarenal aortic diameters. Simvastatin did not favourably modify serum lipids in either mouse model.
In this study involving two mouse models of AAA, simvastatin had limited efficacy in restricting aortic dilatation but substantial ability to reduce atheroma progression.
Key wordsAorta Aneurysm Mouse model Simvastatin Atherosclerosis
Grants from the National Health and Medical Research Council (project grant 379600 and 540404) supported this work. JG is supported by Practitioner Fellowship from the National Health and Medical Research Council, Australia (431503).
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