Plasmalogen modulation attenuates atherosclerosis in ApoE- and ApoE/GPx1-deficient mice

• Oral administration of batyl alcohol increased plasmalogen level in plasma and heart.
• Increased plasmalogen level attenuated atherosclerosis in mice.
• Oxidation of plasmalogen in vivo was evident from the increase of sn-2 lysophospholipids.
• Increased plasmalogen reduced aortic VCAM-1 and nitrotyrosine levels in ApoE/GPx1-deficient mice.
• Altogether the data suggest that plasmalogen attenuate atherosclerosis via inflammation or oxidative pathways.

Background and aimWe 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 resultsSix-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.ConclusionPlasmalogen 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.