Ezetimibe Promotes Brush Border Membrane-to-Lumen Cholesterol Efflux in the Small Intestine
Fig 6
Cholesterol efflux in ABCG5 and ABCG8 double knockout (DKO) mice.
A, Quantitative RT-PCR showed that NPC1L1 gene expression level did not differ apparently with ABCG5/G8 deletions in mice. Gene expressions were normalized against 18s expression levels. Then the relative expression levels were compared between the two genotypes, WT (n 10) and ABCG5/G8 DKO (n 6) with the levels in the WT mice as the references. Data are shown as mean ± SEM. B, Ezetimibe (50 μg)-induced increase in cholesterol efflux was partially abolished in ABCG5/G8 DKO mice. Upper, Plots for 3H-decay per minute (DPM) counts in the perfusate (right, gray circles) and the perfused intestinal segment (left, open circles). Lower; 3H-DPM in the perfusate was divided by that in the intestinal segment perfused to obtain a ratio (%), which was then converted to a common logarithm. Bars indicate medians. The difference between wild-type (WT) and DKO mice was compared using the Student’s t-test. Each plot shows an individual assay result. Alphabetical differences (in parentheses) indicate significant difference between the groups (p < 0.05) using Tukey's Honestly Significant Difference test. C, ABCG5/G8 DKO partially abolished the inhibitory effect of ezetimibe on the intestinal cholesterol transit. Bars indicate medians. Each plot shows an individual assay result. The difference between the WT and the DKO mice was compared using the Mann—Whitney U-test. D, Comparison of mRNA abundance by quantitative RT-PCR between the jejunal samples of C57BL/6J and 129+Ter/SvJ. Data are shown as mean ± SEM (n 5). E, Characteristic comparisons of C57BL/6J and 129+Ter/SvJ mice in luminal perfusion assay. Upper, efflux efficiency; lower, intestinal 3H-DPM abundance. The difference between the two strains was compared using the Mann—Whitney U-test. Bars indicate medians. Each plot shows an individual assay result.