Effects of atorvastatin and/or probucol on recovery of atherosclerosis in high-fat-diet-fed apolipoprotein E–deficient mice

•Atorvastatin exhibits a powerful hypocholesterolemic effect in a high-fat-diet-fed ApoE-/- mouse model of atherosclerosis.•The recovery of atherosclerosis by atorvastatin is involved in suppression of ER stress and the increase in TLR-4 level, which lowers NF-κB.•Combination of atorastain and probucol has shown a slightly stronger effect on the atherosclerosis recovery.•Probucol has significantly shown the add-on anti-atherosclerotic effect in reduction of plaque lesions area and macrophages. We have investigated the possible effects and mechanism of atorvastatin, a statin, and/or probucol, a powerful antioxidant used to lower cholesterol before 1995, on the atherosclerosis development. Apolipoprotein-E-deficient (ApoE−/−) mice fed with the high fat diet were randomly divided into 3 groups (n = 10/each group): Placebo, Atorvastatin (10 mg/ kg/d), and atorvastatin (10 mg/kg/d) plus probucol (10 mg/kg/d) groups. C57BL/6 J mice were fed with normal diet as the control group (n = 10). Animals were sacrificed 10 weeks after the intervention. To evaluate the experimental atherosclerosis, blood tests were used for measuring serum lipoprotein profile, Western blots for endoplasmic reticulum (ER) stress protein expression, H&E staining for plaque lesions, immunohistology for macrophages, inflammatory cytokines, innate immune receptor TLR-4, transcription factor NF-κB, and atherosclerosis plaques. Compared with the control group, ApoE−/− mice in the placebo group showed with the significantly (p