title: Atherosclerosis induced by a high-fat diet is alleviated by lithium chloride via reduction of VCAM expression in ApoE-deficient mice.
abstract: Endothelial cell dysfunction may play an important role in the development of various vascular diseases, including atherosclerosis. Here we investigated whether lithium chloride (LiCl), an inhibitor of glycogen synthase kinase-3β (GSK-3β), could counteract atherosclerosis induced by a high-fat diet in ApoE⁻/⁻ mice. Ten-week-old male mice were randomly divided into four groups: normal chow diet, high-fat diet (i.e., 20% fat and 0.5% cholesterol), high-fat diet with LiCl treatment for 6 weeks and high-fat diet with LiCl treatment for 14 weeks. Examination of plasma profiles indicated that blood glucose levels were significantly decreased by LiCl treatment. Supplementation with LiCl dramatically reduced atherosclerotic lesion formation in the aorta and aortic root. LiCl treatment also decreased vascular cell adhesion molecule (VCAM)-1 expression and macrophage infiltration into atherosclerotic lesion areas within the aortic valve. In addition, inhibition of GSK-3β by TDZD-8, SB216763, and LiCl, as well as adenoviral transduction with a catalytically inactive GSK-3β, reduced palmitate-induced VCAM-1 expression through inhibition of JNK activity and degradation of Iκ-Bα in human umbilical vein endothelial cells (HUVECs). The results of the present study suggest that LiCl alleviates palmitate-induced cell adhesion molecule expression in HUVECs and decreases atherosclerosis induced by a high-fat diet in ApoE⁻/⁻ mice. Thus, GSK-3β may be involved in the development of atherosclerosis induced by a high-fat diet in ApoE⁻/⁻ mice.
authors.affiliation: Department of Endocrinology and Metabolism, Ajou University School of Medicine, Suwon, Kyunggi-do 442-749, Republic of Korea.
authors.forename: Sung-E
authors.initials: SE
authors.lastname: Choi
authors.forename: Hyun-Ju
authors.initials: HJ
authors.lastname: Jang
authors.forename: Yup
authors.initials: Y
authors.lastname: Kang
authors.forename: Jong Gab
authors.initials: JG
authors.lastname: Jung
authors.forename: Seung Jin
authors.initials: SJ
authors.lastname: Han
authors.forename: Hae Jin
authors.initials: HJ
authors.lastname: Kim
authors.forename: Dae Jung
authors.initials: DJ
authors.lastname: Kim
authors.forename: Kwan-Woo
authors.initials: KW
authors.lastname: Lee
mesh_terms: D000818:Animals; D001021:Aortic Valve / Q000378:metabolism; D001057:Apolipoproteins E / Q000235:genetics*; D050197:Atherosclerosis / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D001786:Blood Glucose / Q000378:metabolism; D002478:Cells, Cultured; D004036:Diet, Atherogenic; D004041:Dietary Fats / Q000008:administration & dosage*; D042783:Endothelial Cells / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors* / Q000235:genetics; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D050356:Lipid Metabolism; D018021:Lithium Chloride / Q000494:pharmacology*; D008264:Macrophages / Q000473:pathology; D008297:Male; D008301:Maleimides / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D010168:Palmitates / Q000494:pharmacology; D013830:Thiadiazoles / Q000494:pharmacology; D014471:Umbilical Veins / Q000166:cytology; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*
chemical_list: C494356:4-benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione; D001057:Apolipoproteins E; D001786:Blood Glucose; D004041:Dietary Fats; D007211:Indoles; D008301:Maleimides; D010168:Palmitates; C417521:SB 216763; D013830:Thiadiazoles; D019010:Vascular Cell Adhesion Molecule-1; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3; D018021:Lithium Chloride