Effects of felodipine on atherosclerosis in high cholesterol-diet apolipoprotein E knock-out mice

AIM: To investigate the potential effects and molecular mechanisms of a calcium channel blocker felodipine on the process of atherosclerosis in high cholesterol-diet (HCD) apolipoprotein E knock-out (ApoE KO) mice. METHODS: Adult male ApoE KO mice were given normal diet (ND) or HCD and randomized to normal diet or felodipine 5 mg·kg-1·d-1 for 12 weeks. Systolic blood pressure was measured by a kind of non-invasive tail cuff system in conscious condition. The plasma total cholesterol and triglyceride concentration were measured by autoanalyzer. Atherosclerotic lesion area in arotic root was evaluated by oil red O staining. Inflammatory cytokines were measured by real-time reverse-transcription polymerase chain reaction (PCR) and Western blotting. RESULTS: The ApoE KO mice with HCD were associated with a marked increase in plasma lipid levels, atherosclerotic lesion area, as well as the expressions of tumor necrosis-α, monocyte chemoattactant protein-1 and vascular cell adhesion molecule-1. These changes were suppressed in mice that were treated with felodipine 5 mg·kg-1·d-1 for 12 weeks concomitant with HCD administration. CONCLUSION: The results suggest that felodipine attenuates atherosclerosis. This effect is in part related to inhibition of inflammatory response which leads to the decrease in the expression of inflammatory cytokines.