title: Plasmalogen modulation attenuates atherosclerosis in ApoE- and ApoE/GPx1-deficient mice.
abstract: OBJECTIVE
  We previously reported a negative association of circulating plasmalogens (phospholipids with proposed atheroprotective properties) with coronary artery disease. Plasmalogen modulation was previously demonstrated in animals but its effect on atherosclerosis was unknown. We assessed the effect of plasmalogen enrichment on atherosclerosis of murine models with differing levels of oxidative stress.
  
  
  RESULTS
  Six-week old ApoE- and ApoE/glutathione peroxidase-1 (GPx1)-deficient mice were fed a high-fat diet with/without 2% batyl alcohol (precursor to plasmalogen synthesis) for 12 weeks. Mass spectrometry analysis of lipids showed that batyl alcohol supplementation to ApoE- and ApoE/GPx1-deficient mice increased the total plasmalogen levels in both plasma and heart. Oxidation of plasmalogen in the treated mice was evident from increased level of plasmalogen oxidative by-product, sn-2 lysophospholipids. Atherosclerotic plaque in the aorta was reduced by 70% (P = 5.69E-07) and 69% (P = 2.00E-04) in treated ApoE- and ApoE/GPx1-deficient mice, respectively. A 40% reduction in plaque (P = 7.74E-03) was also seen in the aortic sinus of only the treated ApoE/GPx1-deficient mice. Only the treated ApoE/GPx1-deficient mice showed a decrease in VCAM-1 staining (-28%, P = 2.43E-02) in the aortic sinus and nitrotyrosine staining (-78%, P = 5.11E-06) in the aorta.
  
  
  CONCLUSIONS
  Plasmalogen enrichment via batyl alcohol supplementation attenuated atherosclerosis in ApoE- and ApoE/GPx1-deficient mice, with a greater effect in the latter group. Plasmalogen enrichment may represent a viable therapeutic strategy to prevent atherosclerosis and reduce cardiovascular disease risk, particularly under conditions of elevated oxidative stress and inflammation.
authors.affiliation: Baker IDI Heart and Diabetes Institute, Melbourne, VIC, Australia; Department of Biochemistry and Molecular Biology, The University of Melbourne, Parkville, Australia.
authors.forename: Aliki A
authors.initials: AA
authors.lastname: Rasmiena
authors.affiliation: Baker IDI Heart and Diabetes Institute, Melbourne, VIC, Australia.
authors.forename: Christopher K
authors.initials: CK
authors.lastname: Barlow
authors.affiliation: Baker IDI Heart and Diabetes Institute, Melbourne, VIC, Australia.
authors.forename: Nada
authors.initials: N
authors.lastname: Stefanovic
authors.affiliation: Baker IDI Heart and Diabetes Institute, Melbourne, VIC, Australia.
authors.forename: Kevin
authors.initials: K
authors.lastname: Huynh
authors.affiliation: Baker IDI Heart and Diabetes Institute, Melbourne, VIC, Australia.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Tan
authors.affiliation: Baker IDI Heart and Diabetes Institute, Melbourne, VIC, Australia.
authors.forename: Arpeeta
authors.initials: A
authors.lastname: Sharma
authors.affiliation: Metabolomics Australia, Bio21 Institute, Parkville, Australia.
authors.forename: Dedreia
authors.initials: D
authors.lastname: Tull
authors.affiliation: Baker IDI Heart and Diabetes Institute, Melbourne, VIC, Australia. Electronic address: judy.dehaan@bakeridi.edu.au.
authors.forename: Judy B
authors.initials: JB
authors.lastname: de Haan
authors.affiliation: Baker IDI Heart and Diabetes Institute, Melbourne, VIC, Australia; Department of Biochemistry and Molecular Biology, The University of Melbourne, Parkville, Australia. Electronic address: peter.meikle@bakeridi.edu.au.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Meikle
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D001018:Aortic Diseases / Q000097:blood / Q000201:enzymology / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D050197:Atherosclerosis / Q000097:blood / Q000201:enzymology / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D002784:Cholesterol / Q000097:blood; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D005979:Glutathione Peroxidase / Q000172:deficiency* / Q000235:genetics; D005995:Glyceryl Ethers / Q000378:metabolism / Q000494:pharmacology*; D018836:Inflammation Mediators / Q000378:metabolism; D008246:Lysophospholipids / Q000097:blood; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009206:Myocardium / Q000201:enzymology; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D058226:Plaque, Atherosclerotic; D010955:Plasmalogens / Q000097:blood*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D015854:Up-Regulation; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D000094765:Glutathione Peroxidase GPX1
chemical_list: D001057:Apolipoproteins E; D005995:Glyceryl Ethers; D018836:Inflammation Mediators; D008246:Lysophospholipids; D010955:Plasmalogens; D019010:Vascular Cell Adhesion Molecule-1; C002744:3-nitrotyrosine; C033433:batyl alcohol; D014443:Tyrosine; D002784:Cholesterol; D005979:Glutathione Peroxidase; D000094765:Glutathione Peroxidase GPX1; C000722068:Gpx1 protein, mouse
keywords: Alkenylphospholipid; Alkylphospholipid; Anti-oxidant; Atherosclerosis; Batyl alcohol; Lipidomics; Plasmalogen