Document Detail


Atherosclerosis induced by a high-fat diet is alleviated by lithium chloride via reduction of VCAM expression in ApoE-deficient mice.
MedLine Citation:
PMID:  20888430     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Sung-E Choi; Hyun-Ju Jang; Yup Kang; Jong Gab Jung; Seung Jin Han; Hae Jin Kim; Dae Jung Kim; Kwan-Woo Lee
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-10-01
Journal Detail:
Title:  Vascular pharmacology     Volume:  53     ISSN:  1879-3649     ISO Abbreviation:  Vascul. Pharmacol.     Publication Date:    2010 Nov-Dec
Date Detail:
Created Date:  2010-11-15     Completed Date:  2011-03-28     Revised Date:  2011-11-02    
Medline Journal Info:
Nlm Unique ID:  101130615     Medline TA:  Vascul Pharmacol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  264-72     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Inc. All rights reserved.
Affiliation:
Department of Endocrinology and Metabolism, Ajou University School of Medicine, Suwon, Kyunggi-do 442-749, Republic of Korea.
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MeSH Terms
Descriptor/Qualifier:
Animals
Aortic Valve / metabolism
Apolipoproteins E / genetics*
Atherosclerosis / etiology,  metabolism,  prevention & control*
Blood Glucose / metabolism
Cells, Cultured
Diet, Atherogenic
Dietary Fats / administration & dosage*
Endothelial Cells / metabolism
Glycogen Synthase Kinase 3 / antagonists & inhibitors*,  genetics
Humans
Indoles / pharmacology
Lipid Metabolism
Lithium Chloride / pharmacology*
Macrophages / pathology
Male
Maleimides / pharmacology
Mice
Mice, Knockout
Palmitates / pharmacology
Thiadiazoles / pharmacology
Umbilical Veins / cytology
Vascular Cell Adhesion Molecule-1 / genetics,  metabolism*
Chemical
Reg. No./Substance:
0/4-benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione; 0/Apolipoproteins E; 0/Blood Glucose; 0/Dietary Fats; 0/Indoles; 0/Maleimides; 0/Palmitates; 0/SB 216763; 0/Thiadiazoles; 0/Vascular Cell Adhesion Molecule-1; 7447-41-8/Lithium Chloride; EC 2.7.11.1/glycogen synthase kinase 3 beta; EC 2.7.11.26/Glycogen Synthase Kinase 3

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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