Document Detail


The tryptophan metabolite 3-hydroxyanthranilic acid lowers plasma lipids and decreases atherosclerosis in hypercholesterolaemic mice.
MedLine Citation:
PMID:  22711758     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
AIMS: Cardiovascular disease is the most common cause of death in the world and atherosclerosis, an inflammatory process in the vessel wall, accounts for the majority of these deaths. The tryptophan metabolite 3-hydroxyanthranilic acid (3-HAA) has been shown to inhibit inflammation in different experimental autoimmune disease models. However, the effect of 3-HAA in atherosclerosis has never been explored.
METHODS AND RESULTS: In this study, we used the atherosclerosis prone Ldlr-/- mice, and cell culture experiments to evaluate the role of 3-HAA in atherosclerosis. Eight weeks treatment with 3-HAA significantly reduced the lesion size in the aorta, and modulated local and systemic inflammatory responses. 3-hydroxyanthranilic acid inhibited the uptake of oxLDL by macrophages, an initiating event in the formation of foam cells, a major cellular component of atherosclerotic lesions. Surprisingly, 3-HAA significantly affected plasma cholesterol and triglyceride levels in Ldlr-/- mice, likely due to modulation of signalling through peroxisome proliferator-activated receptors.
CONCLUSION: 3-Hydroxyanthranilic acid inhibits atherosclerosis by regulating lipid metabolism and inflammation, two major components of this disease.
Authors:
Lei Zhang; Olga Ovchinnikova; Andreas Jönsson; Anna M Lundberg; Martin Berg; Göran K Hansson; Daniel F J Ketelhuth
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-06-18
Journal Detail:
Title:  European heart journal     Volume:  33     ISSN:  1522-9645     ISO Abbreviation:  Eur. Heart J.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-08-15     Completed Date:  2012-12-14     Revised Date:  2013-04-16    
Medline Journal Info:
Nlm Unique ID:  8006263     Medline TA:  Eur Heart J     Country:  England    
Other Details:
Languages:  eng     Pagination:  2025-34     Citation Subset:  IM    
Affiliation:
Department of Medicine, Center for Molecular Medicine, L8:03, Karolinska University Hospital, Karolinska Institute, Stockholm SE-17176, Sweden.
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MeSH Terms
Descriptor/Qualifier:
3-Hydroxyanthranilic Acid / pharmacology*
Animals
Atherosclerosis / immunology,  prevention & control*
Diet, High-Fat
Free Radical Scavengers / pharmacology*
Hypercholesterolemia / immunology,  prevention & control*
Hypolipidemic Agents / pharmacology
Immunity, Cellular / drug effects
Immunohistochemistry
Indoleamine-Pyrrole 2,3,-Dioxygenase / metabolism
Lipoproteins, LDL / drug effects,  metabolism
Macrophages / drug effects,  metabolism
Mice
Mice, Inbred Strains
RNA, Messenger / metabolism
Chemical
Reg. No./Substance:
0/Free Radical Scavengers; 0/Hypolipidemic Agents; 0/Indoleamine-Pyrrole 2,3,-Dioxygenase; 0/Lipoproteins, LDL; 0/RNA, Messenger; 0/oxidized low density lipoprotein; 548-93-6/3-Hydroxyanthranilic Acid

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


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