Aliki A Rasmiena1, Christopher K Barlow2, Nada Stefanovic2, Kevin Huynh2, Ricardo Tan2, Arpeeta Sharma2, Dedreia Tull3, Judy B de Haan4, Peter J Meikle5. 1. Baker IDI Heart and Diabetes Institute, Melbourne, VIC, Australia; Department of Biochemistry and Molecular Biology, The University of Melbourne, Parkville, Australia. 2. Baker IDI Heart and Diabetes Institute, Melbourne, VIC, Australia. 3. Metabolomics Australia, Bio21 Institute, Parkville, Australia. 4. Baker IDI Heart and Diabetes Institute, Melbourne, VIC, Australia. Electronic address: judy.dehaan@bakeridi.edu.au. 5. 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.
Abstract
BACKGROUND AND AIM: 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. METHODS AND 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. CONCLUSION: 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.
BACKGROUND AND AIM: 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. METHODS AND 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. CONCLUSION: 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: Piyushkumar A Mundra; Christopher K Barlow; Paul J Nestel; Elizabeth H Barnes; Adrienne Kirby; Peter Thompson; David R Sullivan; Zahir H Alshehry; Natalie A Mellett; Kevin Huynh; Kaushala S Jayawardana; Corey Giles; Malcolm J McConville; Sophia Zoungas; Graham S Hillis; John Chalmers; Mark Woodward; Gerard Wong; Bronwyn A Kingwell; John Simes; Andrew M Tonkin; Peter J Meikle Journal: JCI Insight Date: 2018-09-06
Authors: Sudip Paul; Aliki A Rasmiena; Kevin Huynh; Adam Alexander T Smith; Natalie A Mellett; Karin Jandeleit-Dahm; Graeme I Lancaster; Peter J Meikle Journal: Metabolites Date: 2021-05-06