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In this study, we investigated into the role and mechanism of pravastatin preventing atherosclerosis. Our objection is to provide evidence to the conclusion that pravastatin prevent atherosclerosis induced by high cholesterol.
Mice were bred at a temperature of 22±2°C and in a relative humidity of 55±15%-controlled room environment with a 12-hr light and dark cycles and fed on a diet of food and tap water ad libitum. Evaluation of atherosclerotic lesions by morphology and morphometry. The aortic roots were embedded in paraffin and sequential 5-um sections were sliced through the aortic roots. Paraffin sections were stained with Hematoxylin and Eosin. The whole lumen referred to the area that the residual cavity plus the atherosclerotic lesion. In order to estimate the relative size of the lesions, we measured the ratio of the lesion area compared with that of the whole lumen area and expressed as a ratio in terms as a percentage. Detecting of aortic protein expression by Western Blotting analysis SDS-PAGE and Western blot analysis were performed as previously described on the extracted thoracoabdominal aortas. The serum and thoracoabdominal aorta concentrations of ox-LDL was measured by ELISA. Quantitative data is expressed as mean ± SD.
We determined the size of the atherosclerotic lesion in each group of the mice. The aortic intima of the C57BL/6J mice on a non-cholesterol diet was morphologically normal, however mice in the atherosclerosis group showed advanced atherosclerotic lesions in the aortic root. By contrast, mice in the pravastatin group showed a marked reduction in the size of the aortic lesions.
A high cholesterol diet increased the levels of serum LDL-C and TC, which was not significantly alleviated by pravastatin. Serum levels of LDL-C and TC in the atherosclerotic mice was significantly higher in contrast to that of LDL-C and TC in control mice. But, those concentrations of LDL-C and TC were not significantly different in those mice administered with pravastatin in contrast to atherosclerotic ones.
Pravastatin suppresses ox-LDL concentrations in serum and aorta
The concentrations of ox-LDL in serum and aorta were measured by ELISA. The concentrations of ox-LDL in serum and aorta of apoE-/- mice fed on a diet containing 1.25% cholesterol were significantly increased, compared with the concentrations in C57BL/6J mice fed on a normal diet.
The findings of the present study provide a new mechanism through Which pravastatin can prevent atherosclerosis in apolipoprotein E knockout mice. This provides us with a new therapeutic approach and a clearer insight into the clinical benefits of pravastatin.