Fig. 7
Plasma lipid alterations in APP/PS1/EKI mice lacking hepatocyte-derived apoE. a APOE mRNA levels in liver tissues from 4-month-old APP/PS1-EKI mice were analyzed by qPCR (p < 0.0001, F = 31.60). Post hoc analysis showed a significant difference between Cre+/− and Cre−/− mice in all APOE genotypes (p < 0.0001 for all). b PBS-soluble apoE protein concentration was measured in liver homogenates from the same cohort of mice (p < 0.0001, F = 23.03) Post hoc analysis showed a significant difference between Cre+/− and Cre−/− mice in all APOE genotypes (p < 0.0001 for all). Data for a and b were analyzed by one-way ANOVA, followed by Bonferroni’s post-hoc test for differences between each of the groups. N = 3 males, 2 females in each group. c Plasma apoE levels in male mice were measured by ELISA. There was a significant effect of apoE isoform (F2,49 = 70.97, p < 0.0001) and Cre expression (F1,49 = 51.79, p < 0.0001) with a significant interaction (F2,49 = 7.748, p = 0.0012). Post hoc pair-wise comparisons between Cre+/− and Cre−/− groups found Cre expression significantly decreased plasma apoE levels across apoE isoforms. (apoE2, p < 0.0001; apoE3, p = 0.0112; apoE4, p = 0.0232). (n; E2F: 8 Cre−/−, 12 Cre+/−; E3F: 11 Cre−/−, 12 Cre+/−; E4F: 5 Cre−/−, 8 Cre+/−). d Plasma apoE levels in female mice were measured by ELISA. There was a significant effect of apoE isoform (F1,41 = 43.03, p < 0.0001) and Cre expression (F1,41 = 61.81, p < 0.0001) with a significant interaction (F2,41 = 9.954, p = 0.0003). Post hoc pair-wise comparisons between Cre+/− and Cre−/− groups found Cre expression significantly decreased plasma apoE levels across apoE isoforms. (apoE2, p < 0.0001; apoE3, p = 0.0372; apoE4, p = 0.0025). (n; E2F: 5 Cre−/−, 8 Cre+/−; E3F: 11 Cre−/−, 6 Cre+/−; E4F: 11 Cre−/−, 7 Cre+/−) e Total cholesterol in male mice was quantified. There was a significant effect of apoE isoform (F2,49 = 31.14, p < 0.0001) and Cre expression (F1,49 = 86.12, p < 0.0001) and a significant interaction (F2,49 = 24.10, p < 0.0001). Post hoc pair-wise comparisons between Cre+/− and Cre−/− groups found Cre expression significantly increased plasma cholesterol levels in mice expressing apoE2 (p < 0.0001) or apoE3 (p = 0.0001), but not apoE4 (p = 0.1971). (n; E2F: 8 Cre−/−, 12 Cre+/−; E3F: 11 Cre−/−, 12 Cre+/−; E4F: 4 Cre−/−, 9 Cre+/−). f Total plasma cholesterol in female mice was quantified. There was a significant effect of apoE isoform (F2,41 = 46.39, p < 0.0001) and Cre genotype (F1,41 = 24.31, p < 0.0001) with a significant interaction (F2,41 = 12.59, p < 0.0001). Post hoc pair-wise comparisons between Cre+/− and Cre−/− groups found Cre expression significantly increased plasma cholesterol levels in apoE2-expressing mice (p < 0.0001), but not apoE3 or apoE4-expressing mice. (n; E2F: 5 Cre−/−, 8 Cre+/−; E3F: 10 Cre−/−, 6 Cre+/−; E4F: 11 Cre−/−, 7 Cre+/−) g Total plasma triglycerides in male mice were quantified. There was a significant effect of apoE isoform (F2,48 = 13.31, p < 0.0001) and Cre expression (F1,48 = 36.70, p < 0.0001), with a significant interaction (F2,48 = 3.755, p = 0.0306). Post hoc pairwise comparisons between Cre+/− and Cre−/− groups found Cre expression significantly increased triglyceride levels in mice expressing apoE2 (p < 0.0001) or apoE3 (p = 0.0001), but not apoE4. (n; E2F: 8 Cre−/−, 11 Cre+/−; E3F: 11 Cre−/−, 12 Cre+/−; E4F: 4 Cre−/−, 9 Cre+/−) h Total plasma triglycerides in female mice were quantified. There was a significant effect of apoE isoform (F2,40 = 10.68, p = 0.0002) and Cre expression (F1,40 = 4.168, p = 0.0478), but no significant interaction (F2,40 = 0.1031, p = 0.9023). Post hoc pair-wise comparisons did not identify significant differences in triglyceride levels in mice dependent on Cre expression. (n; E2F: 4 Cre−/−, 8 Cre+/−; E3F: 10 Cre−/−, 6 Cre+/−; E4F: 11 Cre−/−, 7 Cre+/−) i Total plasma HDL in male mice was quantified. There was a significant effect of apoE isoform (F2,49 = 8.239, p = 0.0008), but not Cre expression (F1,49 = 0.9027, p = 0.3467) with a significant interaction (F2,49 = 5.434, p = 0.0074). (n; E2F: 8 Cre−/−, 12 Cre+/−; E3F: 11 Cre−/−, 12 Cre+/−; E4F: 4 Cre−/−, 9 Cre+/−). j Total plasma HDL in female mice was quantified. There was a significant effect of apoE isoform (F2,42 = 9.9098, p = 0.0005), but not Cre expression (F1,42 = 0.9699, p = 0.3304), with no interaction (F2,42 = 1.668, p = 0.2010). (n; E2F: 5 Cre−/−, 8 Cre+/−; E3F: 11 Cre−/−, 6 Cre+/−; E4F: 11 Cre−/−, 7 Cre+/−). Data analyzed by 2-way ANOVA followed by Holm-Sidak multiple comparisons testing. Values from EKO mice are also plotted according to sex (n = 5 males, 3 females), but were not included in statistical comparisons. * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001