Downregulation of Cyp7a1 by Cholic Acid and Chenodeoxycholic Acid in Cyp27a1/ApoE Double Knockout Mice: Differential Cardiovascular Outcome.

Frontiers in Endocrinology
Line ZurkindenGeneviève Escher

Abstract

Sterol 27-hydroxylase (CYP27A1) is a key enzyme in bile acids (BAs) biosynthesis and a regulator of cholesterol metabolism. Cyp27a1/Apolipoprotein E double knockout (DKO) mice fed with western diet (WD) are protected from atherosclerosis via up-regulation of hepatic Cyp7a1 and Cyp3a11. Since feeding BAs ameliorates metabolic changes in Cyp27a1 KO mice, we tested BAs feeding on the development of atherosclerosis in DKO mice. DKO mice were fed for 8 weeks with WD containing 0.1% cholic acid (CA) (WD-CA) or chenodeoxycholic acid (CDCA) (WD-CDCA). Atherosclerotic lesions, plasma lipoprotein composition and functionality, hepatic lipid content, BAs amount and composition, expression of genes involved in lipid metabolism and BA signaling in liver and intestine as well as intestinal cholesterol absorption were assessed. Hepatic Cyp7a1 and Cyp3a11 expression were reduced by 60% after feeding with both WD-CA and WD-CDCA. After feeding with WD-CA we observed a 40-fold increase in the abundance of atherosclerotic lesions in the aortic valve, doubling of the levels of plasma total and low density lipoprotein cholesterol and halving of the level of high density lipoprotein cholesterol. Furthermore, in these mice plasma cholesterol efflux ca...Continue Reading

References

May 26, 1992·Biochemistry·D W Russell, K D Setchell
Jun 9, 1999·Molecular Cell·H WangB M Forman
Jun 16, 2001·American Journal of Physiology. Gastrointestinal and Liver Physiology·E HallW Pandak
Nov 7, 2001·The Journal of Clinical Investigation·C QuattropaniF J Frey
Jan 18, 2003·The Journal of Biological Chemistry·Genevieve EscherDmitri Sviridov
Jan 25, 2003·Annual Review of Biochemistry·David W Russell
Jun 14, 2003·Molecular Endocrinology·Jean Claude OurlinJean Marc Pascussi
Jul 16, 2008·Journal of Lipid Research·Nigora MukhamedovaDmitri Sviridov
Nov 20, 2008·Journal of Lipid Research·David Q-H WangMartin C Carey
Dec 3, 2013·Biochimica Et Biophysica Acta·Ulrich PecksGeneviève Escher
Dec 12, 2013·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Line ZurkindenGeneviève Escher
Jan 15, 2015·Toxicology and Applied Pharmacology·Peizhen SongCurtis D Klaassen
Mar 2, 2017·Digestive Diseases·Frank J GonzalezAndrew D Patterson
Apr 25, 2019·Annual Review of Nutrition·John Y L Chiang, Jessica M Ferrell

❮ Previous
Next ❯

Methods Mentioned

BETA
enzyme-linked immunosorbent assay
PCR

Software Mentioned

ImageJ

Related Concepts

Related Feeds

ApoE Phenotypes

Apolipoprotein E (APOE) is a protein involved in fat metabolism and associated with the pathogenesis of Alzheimer's disease and cardiovascular disease. Here is the latest research on APOE phenotypes.

© 2021 Meta ULC. All rights reserved