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

Aliki A. Rasmiena, Christopher K. Barlow, Nada Stefanovic, Kevin Huynh, Ricardo Tan, Arpeeta Sharma, Dedreia Tull, Judy B. de Haan, Peter J. Meikle

Research output: Contribution to journalArticleResearchpeer-review

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.

Original languageEnglish
Pages (from-to)598-608
Number of pages11
JournalAtherosclerosis
Volume243
Issue number2
DOIs
Publication statusPublished - 1 Dec 2015
Externally publishedYes

Keywords

  • Alkenylphospholipid
  • Alkylphospholipid
  • Anti-oxidant
  • Atherosclerosis
  • Batyl alcohol
  • Lipidomics
  • Plasmalogen

Cite this

Rasmiena, Aliki A. ; Barlow, Christopher K. ; Stefanovic, Nada ; Huynh, Kevin ; Tan, Ricardo ; Sharma, Arpeeta ; Tull, Dedreia ; de Haan, Judy B. ; Meikle, Peter J. / Plasmalogen modulation attenuates atherosclerosis in ApoE- and ApoE/GPx1-deficient mice. In: Atherosclerosis. 2015 ; Vol. 243, No. 2. pp. 598-608.
@article{9f49e5439c01451089112b6bb85f94e8,
title = "Plasmalogen modulation attenuates atherosclerosis in ApoE- and ApoE/GPx1-deficient mice",
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.",
keywords = "Alkenylphospholipid, Alkylphospholipid, Anti-oxidant, Atherosclerosis, Batyl alcohol, Lipidomics, Plasmalogen",
author = "Rasmiena, {Aliki A.} and Barlow, {Christopher K.} and Nada Stefanovic and Kevin Huynh and Ricardo Tan and Arpeeta Sharma and Dedreia Tull and {de Haan}, {Judy B.} and Meikle, {Peter J.}",
year = "2015",
month = "12",
day = "1",
doi = "10.1016/j.atherosclerosis.2015.10.096",
language = "English",
volume = "243",
pages = "598--608",
journal = "Atherosclerosis",
issn = "0021-9150",
publisher = "Elsevier",
number = "2",

}

Plasmalogen modulation attenuates atherosclerosis in ApoE- and ApoE/GPx1-deficient mice. / Rasmiena, Aliki A.; Barlow, Christopher K.; Stefanovic, Nada; Huynh, Kevin; Tan, Ricardo; Sharma, Arpeeta; Tull, Dedreia; de Haan, Judy B.; Meikle, Peter J.

In: Atherosclerosis, Vol. 243, No. 2, 01.12.2015, p. 598-608.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Plasmalogen modulation attenuates atherosclerosis in ApoE- and ApoE/GPx1-deficient mice

AU - Rasmiena, Aliki A.

AU - Barlow, Christopher K.

AU - Stefanovic, Nada

AU - Huynh, Kevin

AU - Tan, Ricardo

AU - Sharma, Arpeeta

AU - Tull, Dedreia

AU - de Haan, Judy B.

AU - Meikle, Peter J.

PY - 2015/12/1

Y1 - 2015/12/1

N2 - 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.

AB - 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.

KW - Alkenylphospholipid

KW - Alkylphospholipid

KW - Anti-oxidant

KW - Atherosclerosis

KW - Batyl alcohol

KW - Lipidomics

KW - Plasmalogen

UR - http://www.scopus.com/inward/record.url?scp=84946041922&partnerID=8YFLogxK

U2 - 10.1016/j.atherosclerosis.2015.10.096

DO - 10.1016/j.atherosclerosis.2015.10.096

M3 - Article

VL - 243

SP - 598

EP - 608

JO - Atherosclerosis

JF - Atherosclerosis

SN - 0021-9150

IS - 2

ER -