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The effect of pomegranate extract on coronary artery atherosclerosis in SR-BI/APOE double knockout mice

  • Aishah Al-Jarallah
    Affiliations
    Department of Biochemistry and Biomedical Sciences, McMaster University, 1280 Main St. W., Hamilton, Ontario, Canada L8S 4L8

    Thrombosis and Atherosclerosis Research Institute, David Braley Research Institute, Hamilton General Hospital Campus, 237 Barton St. E., Hamilton, Ontario, Canada L8L 2X2

    Department of Biochemistry, Faculty of Medicine, Kuwait University, P.O. Box 24 923, 13 110 Safat, Kuwait
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  • Fatima Igdoura
    Affiliations
    Thrombosis and Atherosclerosis Research Institute, David Braley Research Institute, Hamilton General Hospital Campus, 237 Barton St. E., Hamilton, Ontario, Canada L8L 2X2
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  • Yi Zhang
    Affiliations
    Thrombosis and Atherosclerosis Research Institute, David Braley Research Institute, Hamilton General Hospital Campus, 237 Barton St. E., Hamilton, Ontario, Canada L8L 2X2
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  • Christine B. Tenedero
    Affiliations
    Thrombosis and Atherosclerosis Research Institute, David Braley Research Institute, Hamilton General Hospital Campus, 237 Barton St. E., Hamilton, Ontario, Canada L8L 2X2
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  • Elizabeth J. White
    Affiliations
    Department of Biology, McMaster University, 1280 Main St. W., Hamilton, Ontario, Canada L8S 4K1
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  • Melissa E. MacDonald
    Affiliations
    Thrombosis and Atherosclerosis Research Institute, David Braley Research Institute, Hamilton General Hospital Campus, 237 Barton St. E., Hamilton, Ontario, Canada L8L 2X2
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  • Suleiman A. Igdoura
    Affiliations
    Department of Biology, McMaster University, 1280 Main St. W., Hamilton, Ontario, Canada L8S 4K1
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  • Bernardo L. Trigatti
    Correspondence
    Corresponding author. Thrombosis and Atherosclerosis Research Institute (TaARI), David Braley Cardiac Vascular and Stroke Research Institute, Hamilton General Hospital Campus, 237 Barton St. E, Hamilton, Ontario, Canada L8L 2X2. Tel.: +1 905 521 2100x40744; fax: +1 905 575 2646.
    Affiliations
    Department of Biochemistry and Biomedical Sciences, McMaster University, 1280 Main St. W., Hamilton, Ontario, Canada L8S 4L8

    Thrombosis and Atherosclerosis Research Institute, David Braley Research Institute, Hamilton General Hospital Campus, 237 Barton St. E., Hamilton, Ontario, Canada L8L 2X2
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      Abstract

      Objectives

      To examine the effects of pomegranate extract on inflammation and oxidative stress and the development of spontaneous occlusive coronary artery atherosclerosis in the SR-BI/apoE double knockout mouse model of coronary heart disease.

      Methods and results

      SR-BI/apoE double KO mice were treated for two weeks with pomegranate extract via drinking water, beginning at three weeks of age. Treatment with pomegranate extract increased cholesterol ester content and reduced the abnormally high unesterified/esterified cholesterol ratio of VLDL-sized lipoproteins. Despite the increase in cholesterol levels associated with VLDL-sized particles, pomegranate extract treatment reduced the size of atherosclerotic plaques in the aortic sinus and reduced the proportion of coronary arteries with occlusive atherosclerotic plaques. Treatment with pomegranate extract resulted in substantial reductions in levels of oxidative stress and monocyte chemotactic protein-1 in atherosclerotic plaques in the aortic sinus and coronary arteries. In addition, treatment with pomegranate extract reduced lipid accumulation, macrophage infiltration, levels of monocyte chemotactic protein-1 and fibrosis in the myocardium, attenuated cardiac enlargement and the development of ECG abnormalities in SR-BI/apoE double KO mice.

      Conclusion

      Pomegranate extract reduced aortic sinus and coronary artery atherosclerosis in SR-BI/apoE dKO mice. The atheroprotective effects of pomegranate extract appear to involve reduced oxidative stress and inflammation in the vessel wall despite unaltered systemic markers of inflammation and increased lipoprotein cholesterol in these mice.

      Highlights

      • SR-BI/apoE dKO mice develop CA atherosclerosis and MI between 3 and 5 weeks of age.
      • Pomegranate extract reduces ROS and inflammation in vessels and hearts of dKO mice.
      • Pomegranate extract reduces CA atherosclerosis and MI in dKO mice.

      Keywords

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