Efficacy of simvastatin in reducing aortic dilatation in mouse models of abdominal aortic aneurysm.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
In this study involving two mouse models of AAA, simvastatin had limited efficacy in restricting aortic dilatation but substantial ability to reduce atheroma progression.
Golledge
Jonathan
J
The Vascular Biology Unit, Department of Surgery, School of Medicine, James Cook University, Townsville, QLD, Australia. jonathan.golledge@jcu.edu.au
Cullen
Bradford
B
Moran
Corey
C
Rush
Catherine
C
D000804:Angiotensin II; D000818:Animals; D001012:Aorta, Abdominal / Q000187:drug effects*; D001013:Aorta, Thoracic / Q000187:drug effects / Q000473:pathology; D017544:Aortic Aneurysm, Abdominal / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D008055:Lipids / Q000097:blood; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D058226:Plaque, Atherosclerotic / Q000188:drug therapy / Q000473:pathology; D018110:Receptors, Lipoprotein / Q000172:deficiency / Q000235:genetics; D019821:Simvastatin / Q000494:pharmacology*
D001057:Apolipoproteins E; D008055:Lipids; D018110:Receptors, Lipoprotein; D000804:Angiotensin II; D019821:Simvastatin