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Modulation of atherogenic lipidome by cigarette smoke in apolipoprotein E-deficient mice.
MedLine Citation:
PMID:  23102783     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
OBJECTIVE: Although relationships between smoking and cardiovascular diseases (CVD), and between CVD and lipids are established, the direct impact of smoking on lipidomes is not well understood. We investigated the effect of mainstream cigarette smoke (CS) exposure on plasma, liver, and aorta molecular lipid profiles, and liver transcriptome in the ApoE(-/-) mouse, a well-established mouse model for human atherogenesis. METHODS: Plasma, liver, and aorta samples from ApoE(-/-) mice exposed to CS or fresh air (sham) for six months were extracted for lipids using robotic-assisted method and analyzed by mass spectrometry. Gene expression in the liver was obtained on microarrays. Development of atherosclerosis in the aorta was further assessed by plaque size in the aortic arch and lipoprotein concentration in plasma and plaque. RESULTS: CS increased most lipid classes and molecular lipid species. In plasma, free cholesterol, ceramides, cerebrosides, and most phospholipids were increased in CS-exposed mice. In the liver, several lipid species including free and esterified cholesterol, triacylglycerols, phospholipids, sphingomyelins, and ceramides were elevated. In the aorta, more than 2-fold higher cholesteryl ester (CE), lysophosphatidylcholine, and glucosyl/galactosylceramide levels were seen. Moreover, CS exposure induced a significant decrease in several plasma CE and phosphatidylcholine species that contained polyunsaturated fatty acids. Genes involved in amino acid and lipid metabolism showed perturbed transcription profiles in the liver. CONCLUSION: We have quantified some of the molecular changes that accompany the increase of plaque size that is accelerated by CS exposure in the aortae of ApoE(-/-) mice. These results suggest that specific changes in the lipidome and transcriptome, for example in ceramide and polyunsaturated fatty acid species, may be associated with atherosclerosis.
Authors:
Stéphanie Boué; Kirill Tarasov; Minna Jänis; Stefan Lebrun; Reini Hurme; Walter Schlage; Michael Lietz; Gregory Vuillaume; Kim Ekroos; Yvonne Steffen; Manuel C Peitsch; Reijo Laaksonen; Julia Hoeng
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-10-10
Journal Detail:
Title:  Atherosclerosis     Volume:  -     ISSN:  1879-1484     ISO Abbreviation:  Atherosclerosis     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-29     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0242543     Medline TA:  Atherosclerosis     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
Affiliation:
Philip Morris International R&D, Quai Jeanrenaud 5, CH-2000 Neuchâtel, Switzerland. Electronic address: Stephanie.Boue@pmi.com.
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