Pravastatin attenuates atherosclerosis after myocardial infarction by inhibiting inflammatory Ly6C(high) monocytosis in apolipoprotein E knockout mice

OBJECTIVE: To evaluate the protective effect of pravastatin on atherosclerotic development and inflammatory monocyte subset in atherosclerotic apolipoprotein E (ApoE)(−/−) mice after myocardial infarction (MI). METHODS: Male ApoE(−/−) mice (8 weeks old) were fed a high-fat diet for 14 weeks throughout the experiment. A MI model was produced using 18-week-old ApoE(−/−) mice. They were randomly divided into three groups: sham group, MI group, and MI+Pra group (40 mg/kg/day pravastatin). After 4 weeks (at the end of the study period), the mice were sacrificed and cardiac function was evaluated by echocardiography. Aortic lesion areas were evaluated using oil red O staining. Plaque macrophage in aortic sinus was analyzed by immunofluorescence staining. Flow cytometry was used to explore the proportions of monocyte subsets in the blood, spleen, and bone marrow． RESULTS: Pravastatin improved cardiac function and reduced lesion areas. It also attenuated the supply of monocytes in spleen, especially the inflammatory Ly6C(high) monocyte subset. Pravastatin also subsequently reduced macrophage accumulation in atherosclerotic lesions. CONCLUSIONS: MI accelerated chronic atherosclerosis progress. Pravastatin suppressed atherosclerotic development and inhibited inflammatory monocytosis after MI in ApoE(−/−) mice.