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- W2118433395 abstract "Interruption of the enterohepatic circulation of bile acids induces hepatic bile acid synthesis, increases hepatic cholesterol demand, and increases clearance of apoB-containing lipoproteins in plasma. Based on these effects, bile acid sequestrants have been used for many years to treat hypercholesterolemia and the associated atherosclerosis. The objective of this study was to determine the effect of blocking ileal apical versus basolateral membrane bile acid transport on the development of hypercholesterolemia and atherosclerosis in mouse models.ApoE(-/-) and Ldlr(-/-) mice deficient in the apical sodium-dependent bile acid transporter (Asbt) or apoE(-/-) mice deficient in the basolateral bile acid transporter (Ostα) were fed an atherogenic diet for 16 weeks. Bile acid metabolism, cholesterol metabolism, gene expression, and development of atherosclerosis were examined. Mice deficient in Asbt exhibited the classic response to interruption of the enterohepatic circulation of bile acids, including significant reductions in hepatic and plasma cholesterol levels, and reduced aortic cholesteryl ester content. Ileal Fibroblast Growth Factor-15 (FGF15) expression was significantly reduced in Asbt(-/-)apoE(-/-) mice and was inversely correlated with expression of hepatic cholesterol 7-hydroxylase (Cyp7a1). Ileal FGF15 expression was directly correlated with plasma cholesterol levels and aortic cholesterol content. In contrast, plasma and hepatic cholesterol levels and atherosclerosis development were not reduced in apoE(-/-) mice deficient in Ostα.Decreases in ileal FGF15, with subsequent increases in hepatic Cyp7a1 expression and bile acid synthesis appear to be necessary for the plasma cholesterol-lowering and atheroprotective effects associated with blocking intestinal bile acid absorption." @default.
- W2118433395 created "2016-06-24" @default.
- W2118433395 creator A5008192875 @default.
- W2118433395 creator A5042075065 @default.
- W2118433395 creator A5042218537 @default.
- W2118433395 date "2013-08-01" @default.
- W2118433395 modified "2023-09-26" @default.
- W2118433395 title "Inhibition of ileal apical but not basolateral bile acid transport reduces atherosclerosis in apoE−/− mice" @default.
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- W2118433395 doi "https://doi.org/10.1016/j.atherosclerosis.2013.05.017" @default.
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