title: Addition of aspirin to a fish oil-rich diet decreases inflammation and atherosclerosis in ApoE-null mice.
abstract: Aspirin (ASA) is known to alter the production of potent inflammatory lipid mediators, but whether it interacts with omega-3 fatty acids (FAs) from fish oil to affect atherosclerosis has not been determined. The goal was to investigate the impact of a fish oil-enriched diet alone and in combination with ASA on the production of lipid mediators and atherosclerosis. ApoE(-/-) female mice were fed for 13weeks one of the four following diets: omega-3 FA deficient (OD), omega-3 FA rich (OR) (1.8g omega-3 FAs/kg·diet per day), omega-3 FA rich plus ASA (ORA) (0.1g ASA/kg·diet per day) or an omega-3 FA deficient plus ASA (ODA) with supplement levels equivalent to human doses. Plasma lipids, atherosclerosis, markers of inflammation, hepatic gene expression and aortic lipid mediators were determined. Hepatic omega-3 FAs were markedly higher in OR (9.9-fold) and ORA (7-fold) groups. Mice in both OR and ORA groups had 40% less plasma cholesterol in very low-density lipoprotein-cholesterol and low-density lipoprotein fractions, but aortic plaque area formation was only significantly lower in the ORA group (5.5%) compared to the OD group (2.5%). Plasma PCSK9 protein levels were approximately 70% lower in the OR and ORA groups. Proinflammatory aortic lipid mediators were 50%-70% lower in the ODA group than in the OD group and more than 50% lower in the ORA group. In summary, less aortic plaque lesions and aortic proinflammatory lipid mediators were observed in mice on the fish oil diet plus ASA vs. just the fish oil diet.
authors.affiliation: Lipoprotein Metabolism Section, Cardio-Pulmonary Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Sorokin
authors.affiliation: Lipoprotein Metabolism Section, Cardio-Pulmonary Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Zhi-Hong
authors.initials: ZH
authors.lastname: Yang
authors.affiliation: Lipoprotein Metabolism Section, Cardio-Pulmonary Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Boris L
authors.initials: BL
authors.lastname: Vaisman
authors.affiliation: Lipoprotein Metabolism Section, Cardio-Pulmonary Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Seth
authors.initials: S
authors.lastname: Thacker
authors.affiliation: Pathology Core, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Zu-Xi
authors.initials: ZX
authors.lastname: Yu
authors.affiliation: Clinical Center, Department of Laboratory Medicine, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Maureen
authors.initials: M
authors.lastname: Sampson
authors.affiliation: Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative, and Pain Medicine, Harvard Institutes of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Charles N
authors.initials: CN
authors.lastname: Serhan
authors.affiliation: Lipoprotein Metabolism Section, Cardio-Pulmonary Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA. Electronic address: aremaley1@nhlbi.nih.gov.
authors.forename: Alan T
authors.initials: AT
authors.lastname: Remaley
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000627:therapeutic use*; D001011:Aorta / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism; D001241:Aspirin / Q000009:adverse effects / Q000627:therapeutic use*; D050197:Atherosclerosis / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D066026:Endothelial Progenitor Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015525:Fatty Acids, Omega-3 / Q000009:adverse effects / Q000097:blood / Q000378:metabolism / Q000627:therapeutic use; D005260:Female; D005395:Fish Oils / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*; D005786:Gene Expression Regulation / Q000187:drug effects; D018836:Inflammation Mediators / Q000097:blood; D050356:Lipid Metabolism / Q000187:drug effects; D008055:Lipids / Q000097:blood; D008099:Liver / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018345:Mice, Knockout; D000071449:Proprotein Convertase 9 / Q000097:blood; D011897:Random Allocation; D015430:Weight Gain / Q000187:drug effects
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D001057:Apolipoproteins E; D015415:Biomarkers; D015525:Fatty Acids, Omega-3; D005395:Fish Oils; D018836:Inflammation Mediators; D008055:Lipids; C472126:Pcsk9 protein, mouse; D000071449:Proprotein Convertase 9; D001241:Aspirin
keywords: Aspirin; Atherosclerosis; Fish oil; Inflammation; Omega-3 fatty acids