The tryptophan metabolite 3-hydroxyanthranilic acid lowers plasma lipids and decreases atherosclerosis in hypercholesterolaemic mice.
OBJECTIVE
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.


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.


CONCLUSIONS
3-Hydroxyanthranilic acid inhibits atherosclerosis by regulating lipid metabolism and inflammation, two major components of this disease.
Department of Medicine, Center for Molecular Medicine,  L8:03, Karolinska University Hospital, Karolinska Institute, Stockholm SE-17176,  Sweden.
Lei
L
Zhang
Olga
O
Ovchinnikova
Andreas
A
Jönsson
Anna M
AM
Lundberg
Martin
M
Berg
Göran K
GK
Hansson
Daniel F J
DF
Ketelhuth
D015095:3-Hydroxyanthranilic Acid / Q000494:pharmacology*; D000818:Animals; D050197:Atherosclerosis / Q000276:immunology / Q000517:prevention & control*; D059305:Diet, High-Fat; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006937:Hypercholesterolemia / Q000276:immunology / Q000517:prevention & control*; D000960:Hypolipidemic Agents / Q000494:pharmacology; D007111:Immunity, Cellular / Q000187:drug effects; D007150:Immunohistochemistry; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000187:drug effects / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D012333:RNA, Messenger / Q000378:metabolism
D016166:Free Radical Scavengers; D000960:Hypolipidemic Agents; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D008077:Lipoproteins, LDL; D012333:RNA, Messenger; C099252:oxidized low density lipoprotein; D015095:3-Hydroxyanthranilic Acid