Fig. 6.

Cmpd 81 prevents lovastatin-induced HMGCR accumulation and ameliorates diet-induced hyperlipidemia and atherosclerosis. a Immunoblotting and quantification of HMGCR protein from CHO-7 cells. Data are from three independent experiments. b Male C57BL/6J mice (n = 3 per group) fed on chow diet were gavaged once daily with Cmpd 81 (60 mg/kg/day) with or without lovastatin (60 mg/kg/day) for 10 days. HMGCR proteins from liver membrane fractions were analyzed and quantified by immunoblotting. c–g Male C57BL/6J mice (n = 5 per group) fed with chow diet or medium fat medium cholesterol (MFMC) diet, were gavaged once daily with Cmpd 81 (60 mg/kg/day) with or without lovastatin (60 mg/kg/day) for 6 weeks. Blood and livers were harvested and examined for total cholesterol (TC) levels in the serum (c), triglyceride (TG) levels in the serum (d), TC levels in liver (e), TG levels in liver (f), and lipoprotein profiles of cholesterol levels in pooled serum using FPLC analysis (g). h–j Male Ldlr^−/− mice (n = 5 per group) fed on western diet (WD) were gavaged once daily with indicated Cmpd 81 (60 mg/kg/day) and lovastatin (60 mg/kg/day) for 20 weeks. h FPLC analysis of cholesterol contents in different lipoproteins. i Representative en face Sudan IV staining of aortas. Scale bar, 200 μm. j Quantifications of atherosclerotic lesions shown in i. Data are presented as mean ± SD. P values were determined by one-way ANOVA followed by Dunnett’s multiple comparisons test. ^*P < 0.05, ^**P < 0.01, ^***P < 0.001, ^#P < 0.05. Source data are provided as a Source Data File. Uncropped immunoblots are shown in Supplementary Fig. 10