OBJECTIVETo investigate the effects of simvastatin on atherosclerosis and central aortic pressure in ApoE-knockout (ApoE-/-) mice.

METHODSTen 5-week-old male ApoE-/- mice and 5 C57 mice were fed with high-lipid diet for 3 weeks, and then C57 mice (WT group) and 5 ApoE-/- mice (ApoE-/- group) were given 1% carboxymethyl cellulose solution (8 ml·kg-1·d-1), and another 5 ApoE-/- mice (ApoE-/-/S group) were given simvastatin solution (50 mg·kg-1·d-1) by gavege for 3 weeks. The areas of atherosclerotic lesion in aortic root, central aortic pressure and serum lipid levels were examined.

RESULTSNo atherosclerotic plaques were observed in WT group. Compared with ApoE-/- group, simvastatin significantly decreased atherosclerotic lesion area in aortic root (89 818.05±16 980.93 μm2 vs 34 937.01±13 280.65 μm2, P<0.05). The systolic pressure (SP), mean arterial pressure (MAP), pulse pressure (PP) and diastolic pressure (DP) of central aortic pressure were significantly increased in ApoE-/- group compared with those in WT group (P<0.05). Compared to ApoE-/- group, the SP, MAP and PP of central aortic pressure were significantly reduced in ApoE-/-/S group (P<0.05). SP and MAP of central aortic pressure were positively correlated with atherosclerotic lesion area (SP: r=0.7152, P=0.0461; PP: r=0.7594， P=0.0288). Compared with WT group, serum triglyceride, total cholesterol and low-density lipoprotein levels were markedly increased in ApoE-/- group (P<0.05). Serum high-density lipoprotein level was decreased in ApoE-/- group compared with WT group. No differences in serum triglyceride, total cholesterol, low-density lipoprotein and high-density lipoprotein levels were found between ApoE-/- group and ApoE-/-/S group.

CONCLUSIONSimvastatin can attenuate atherosclerosis of aorta in ApoE-/- mice, which is associated with the reduced central aortic systolic pressure but not with the serum lipids levels.