Document Detail

Effect of 2-amino-9H-pyrido[2,3-b]indole (AalphaC), a carcinogenic heterocyclic amine present in food, on atherosclerotic plaque development in apoE deficient mice.
MedLine Citation:
PMID:  19103270     Owner:  NLM     Status:  MEDLINE    
There is experimental and epidemiological evidence demonstrating that polycyclic aromatic hydrocarbons (PAHs) are involved in the pathogenesis of cardiovascular diseases. However, heterocyclic amines (HAs), a class of carcinogenic compounds present in food, which share many biochemical features with PAHs, have not received much attention. Previous reports have shown that the heterocyclic amine 2-amino-9H-pyrido[2,3-b]indole (AalphaC) binds and metabolically affects endothelial cells in animal models suggesting a potential role in vascular remodeling. The present study investigates the effect of exposure to HAs on atherosclerotic plaque development in the apoE(-/-) mice. We observed that animals treated with AalphaC developed atherosclerotic lesions characterized by lower lipid content but richer in inflammatory cells and collagen content when compared with control animals. Moreover, atherosclerotic plaques from AalphaC-treated apoE(-/-) mice were also smaller with a marked reduction in the tunica media thickness. Furthermore, total cholesterol levels were significantly reduced in AalphaC-treated apoE(-/-) mice. In contrast to what has been previously reported for PAHs, we provide for the first time evidence that HAs may protect against cardiovascular disease by inducing stable atherosclerotic plaques and reducing circulating cholesterol levels. These results open new avenues to further investigate the role of these food-borne carcinogens in cardiovascular physiology and pathology.
Carlos Lopez-Mendez; Alexandra Bermudez-Fajardo; Costas Ioannides; Ernesto Oviedo-Orta
Publication Detail:
Type:  Journal Article     Date:  2008-12-03
Journal Detail:
Title:  Toxicology letters     Volume:  185     ISSN:  0378-4274     ISO Abbreviation:  Toxicol. Lett.     Publication Date:  2009 Mar 
Date Detail:
Created Date:  2009-02-09     Completed Date:  2009-04-06     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7709027     Medline TA:  Toxicol Lett     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  73-8     Citation Subset:  IM    
University of Surrey, Faculty of Heath and Medical Sciences, Guildford GU2 7XH, Surrey, United Kingdom.
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MeSH Terms
Aorta, Abdominal / drug effects,  metabolism,  pathology
Apolipoproteins E / deficiency*,  genetics
Atherosclerosis / chemically induced*,  genetics,  metabolism,  pathology
Body Weight / drug effects
Carbolines / toxicity*
Carcinogens / toxicity*
Food Contamination*
Lipids / blood
Mice, Knockout
Reg. No./Substance:
0/Apolipoproteins E; 0/Carbolines; 0/Carcinogens; 0/Lipids; 26148-68-5/2-amino-9H-pyrido(2,3-b)indole

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