FIG 8.

miR-27a diminishes Hmgcr and plasma lipid levels in high-cholesterol-diet-fed Apoe^−/− mice. (A) Male Apoe^−/− mice (8 to 10 weeks old) were fed a high-cholesterol diet (HCD) regimen for 10 weeks, injected with either the miR-27a mimic or the control oligonucleotide twice over a period of 11 days, and then euthanized. (B) qPCR for miR-27a levels in various tissues. (C) Western blot analysis of Hmgcr protein in Apoe^−/− mouse liver tissues (n = 4 in each group). Data are representative of results from three experiments. (D) Hmgcr protein levels were normalized to vinculin levels (shown in the bar plot). The blot shown is representative of results from three experiments. (E) Lipids were extracted from liver tissue, and hepatic cholesterol levels were measured in control oligonucleotide- and miR-27a-injected Apoe^−/− mice. (F to I) Plasma levels of total cholesterol (F), LDL cholesterol (G), triglycerides (H), and HDL cholesterol (I) from animals fasted overnight. (J to L) Plasma ALT (J), AST (K), and CK (L) levels were also measured. Data are means ± SEM (n = 5 to 6 animals per group). U/l, units per liter. Statistical significance was determined by Student’s t test (unpaired, 2 tailed). *, P < 0.05; **, P < 0.01; ***, P < 0.001 (compared to the control group).