title: Cigarette-smoke-induced atherogenic lipid profiles in plasma and vascular tissue of apolipoprotein E-deficient mice are attenuated by smoking cessation.
abstract: Tobacco smoke exerts perturbations on lipid metabolism and arterial cell function that accelerate atherosclerosis. Lipidomics has emerged as a key technology in helping to elucidate the lipid-related mechanisms of atherosclerosis. In this study, we investigated the effects of smoking cessation on plaque development and aortic arch content of various lipid molecular classes and species. Apolipoprotein E-deficient mice were exposed to fresh air (sham) or to mainstream cigarette smoke (CS) for 6 months, or to CS for 3 months followed by sham for 3 months (cessation group). Lipids from plasma and aortic arches, plasma lipoprotein profiles and plaque morphometry measurements were analyzed. We already showed that CS exposure accelerated plaque size and total cholesterol content of the aortic arch at 3 and 6 months. Marked increases were seen in the relative enrichment of cholesteryl esters, phospholipids, sphingomyelins, and glycosphingolipids. Smoking cessation slowed plaque progression and resulted in lower levels of many lipid species in plasma and aortic arch. While CS exposure promoted rapid lipid accumulation in mouse aorta, smoking cessation translated into a slow removal of lipids from the vessel wall. Despite the smoking cessation-dependent metabolic changes leading to increased animal body weight, accumulation of proatherogenic lipids in the vessel was halted after exposure cessation, indicating that the clinical benefits of smoking cessation translate directly to the vessel wall and its lipid makeup.
authors.affiliation: Philip Morris International R&D, Philip Morris Research Laboratories GmbH, Cologne, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Lietz
authors.forename: An
authors.initials: A
authors.lastname: Berges
authors.forename: Stefan
authors.initials: S
authors.lastname: Lebrun
authors.forename: Kris
authors.initials: K
authors.lastname: Meurrens
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Steffen
authors.forename: Katrin
authors.initials: K
authors.lastname: Stolle
authors.forename: Jutta
authors.initials: J
authors.lastname: Schueller
authors.forename: Stephanie
authors.initials: S
authors.lastname: Boue
authors.forename: Grégory
authors.initials: G
authors.lastname: Vuillaume
authors.forename: Patrick
authors.initials: P
authors.lastname: Vanscheeuwijck
authors.forename: Michaela
authors.initials: M
authors.lastname: Moehring
authors.forename: Walter
authors.initials: W
authors.lastname: Schlage
authors.forename: Hector
authors.initials: H
authors.lastname: De Leon
authors.forename: Julia
authors.initials: J
authors.lastname: Hoeng
authors.forename: Manuel
authors.initials: M
authors.lastname: Peitsch
mesh_terms: D000818:Animals; D001018:Aortic Diseases / Q000378:metabolism / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics*; D050197:Atherosclerosis / Q000378:metabolism* / Q000473:pathology; D001835:Body Weight / Q000502:physiology; D002784:Cholesterol / Q000097:blood; D004195:Disease Models, Animal; D005260:Female; D006028:Glycosphingolipids / Q000378:metabolism; D050356:Lipid Metabolism / Q000502:physiology; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000097:blood; D051379:Mice; D018345:Mice, Knockout; D012907:Smoking / Q000009:adverse effects* / Q000378:metabolism*; D016540:Smoking Cessation; D013109:Sphingomyelins / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; D006028:Glycosphingolipids; D008055:Lipids; D008074:Lipoproteins; D013109:Sphingomyelins; D002784:Cholesterol