Inhibition of soluble epoxide hydrolase in mice promotes reverse cholesterol transport and regression of atherosclerosis

Atherosclerosis
Li ShenBruce D Hammock

Abstract

Adipose tissue is the body largest free cholesterol reservoir and abundantly expresses ATP binding cassette transporter A1 (ABCA1), which maintains plasma high-density lipoprotein (HDL) levels. HDLs have a protective role in atherosclerosis by mediating reverse cholesterol transport (RCT). Soluble epoxide hydrolase (sEH) is a cytosolic enzyme whose inhibition has various beneficial effects on cardiovascular disease. The sEH is highly expressed in adipocytes, and it converts epoxyeicosatrienoic acids (EETs) into less bioactive dihydroxyeicosatrienoic acids. We previously showed that increasing EETs levels with a sEH inhibitor (sEHI) (t-AUCB) resulted in elevated ABCA1 expression and promoted ABCA1-mediated cholesterol efflux from 3T3-L1 adipocytes. The present study investigates the impacts of t-AUCB in mice deficient for the low density lipoprotein (LDL) receptor (Ldlr(-/-) mice) with established atherosclerotic plaques. The sEH inhibitor delivered in vivo for 4 weeks decreased the activity of sEH in adipose tissue, enhanced ABCA1 expression and cholesterol efflux from adipose depots, and consequently increased HDL levels. Furthermore, t-AUCB enhanced RCT to the plasma, liver, bile and feces. It also showed the reduction of pla...Continue Reading

References

Sep 27, 1994·Proceedings of the National Academy of Sciences of the United States of America·A S PlumpJ L Breslow
Jan 15, 2000·Journal of the American College of Cardiology·C J VaughanC T Basson
Nov 6, 2003·JAMA : the Journal of the American Medical Association·Steven E NissenRichard Kerensky
Mar 8, 2005·Progress in Lipid Research·John W NewmanBruce D Hammock
Apr 21, 2005·The Journal of Clinical Investigation·Jenelle M TimminsJohn S Parks
Mar 18, 2006·The Journal of Clinical Investigation·Liam R BrunhamMichael R Hayden
May 30, 2006·Analytical Biochemistry·Nicola M WolfBruce D Hammock
Jul 10, 2007·Journal of Medicinal Chemistry·Sung Hee HwangBruce D Hammock
Nov 10, 2007·The Journal of Clinical Investigation·Laurent Yvan-CharvetAlan R Tall
Mar 20, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Joanna M KarasinskaMichael R Hayden
Aug 1, 2009·Obesity·Bart M De TaeyeDouglas E Vaughan
Mar 10, 2010·Circulation·YuZhen ZhangMuredach P Reilly
May 5, 2010·The Journal of Pharmacology and Experimental Therapeutics·Pengcheng LuoMong-Heng Wang
May 15, 2010·Science·Katey J RaynerCarlos Fernández-Hernando
Feb 22, 2011·Journal of Lipid Research·Priya MalikJonathan D Smith
Dec 16, 2011·Journal of Medicinal Chemistry·Hong C Shen, Bruce D Hammock

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Citations

Jan 29, 2016·International Journal of Cardiology·Qiong LiuDan-yan Xu
Dec 2, 2015·Journal of Diabetes·Jinlong HeDing Ai
May 27, 2016·Proceedings of the National Academy of Sciences of the United States of America·Derek W GilroyDavid Bishop-Bailey
Feb 13, 2019·Nutrients·Karsten-H WeylandtUrsula Kassner
Nov 3, 2016·The Proceedings of the Nutrition Society·A E MorganM T Mc Auley
Aug 23, 2019·Journal of Cellular and Molecular Medicine·Chih-Chan LienTzong-Shyuan Lee
Dec 12, 2017·BioMed Research International·Tang-Bin ZouHong-Fu Wu
Nov 2, 2019·Circulation Journal : Official Journal of the Japanese Circulation Society·Hongchun PengDanyan Xu
Jun 18, 2018·Current Hypertension Reports·Olga E Redina, Arcady L Markel
Jan 4, 2020·Prostaglandins & Other Lipid Mediators·Laila R B Dos Santos, Ingrid Fleming
Dec 29, 2020·Journal of Medicinal Chemistry·Cheng-Peng SunXiao-Chi Ma
Jun 22, 2019·ACS Medicinal Chemistry Letters·Kerstin HiesingerEwgenij Proschak
Aug 28, 2021·Journal of Clinical Medicine·Zohaib IqbalAdrian H Heald

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