Effect of simvastatin on the atherosclerotic plaque stability and the angiogenesis in the atherosclerotic plaque of rabbits

Abstract

In this study, the effect of simvastatin on the atherosclerotic plaque stability and the angiogenesis in the atherosclerotic plaque of rabbits was observed. Thirty New Zealand rabbits were randomly divided into the normal control group, the model control group and the simvastatin group, 10 in each group. Rabbits in the normal control group were fed with normal forage, while rabbits in the rest two groups were fed with high fat forage. The balloon injury was performed two weeks later to establish an abdominal aortic atherosclerosis model, and then high fat forage was successively fed to them. Meanwhile, simvastatin at the daily dose of 2.5 mg/kg body weight was administered to rabbits in the simvastatin group. After 6 weeks of successive administration, levels of blood lipids were measured after blood sampling, and the serum high sensitivity C-reactive protein (hsCRP) and matrix metalloproteinase-3,-9 (MMP-3,-9) were detected using enzyme-linked immunosorbent assay. The macroscopically pathological indices of the plaque tissue were observed using hematoxylin and eosin (HE) staining of abdominal aorta specimens under a light microscope, and the plaque area (PA), cross-sectional vascular area (CVA) and correcting plaque area (PA/CVA) were determined quantitatively using imaging software. The protein expressions of the vascular endothelial growth factor (VEGF), factor VIII related antigen (FVIIIRAg), MMP-3 and cluster of differentiation antigen 40 ligand (CD40L) in the plaque were detected with the immunohistochemical method. Compared with the model control group, the levels of VEGF, FVIIIRAg, MMP-3, CD40L protein expression and the serum expression levels of hsCRP, MMP-3, MMP-9 in the simvastatin group were significantly reduced (P<0.05, P<0.01). The ratio PA/CVA in the simvastatin group was more significantly reduced when compared with that in the model control group (P<0.01). The levels of serum total cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholesterol (LDL) were significantly reduced in the simvastatin group when compared with those in the model control group (P<0.05, P<0.01). Simvastatin plays a certain role in stabilizing the atherosclerotic plaque, and inhibiting the angiogenesis in the atherosclerotic plaque may be one of possible mechanisms.