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Localized vessel expression of lipoprotein lipase in rabbits leads to rapid lipid deposition in the balloon-injured arterial wall

  • Author Footnotes
    1 These authors contributed equally to this work.
    Xiaojun Wu
    Footnotes
    1 These authors contributed equally to this work.
    Affiliations
    Institute of Cardiovascular Sciences, Peking University Health Science Center, 38 XueYuan Road, HaiDian District, Beijing 100083, China

    Department of Cardiology, Beijing Third Hospital, Peking University Health Science Center, Beijing 100083, China
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  • Author Footnotes
    1 These authors contributed equally to this work.
    Jinyu Wang
    Footnotes
    1 These authors contributed equally to this work.
    Affiliations
    Institute of Cardiovascular Sciences, Peking University Health Science Center, 38 XueYuan Road, HaiDian District, Beijing 100083, China

    Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Peking University Health Science Center, Beijing 100083, China
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  • Jianglin Fan
    Affiliations
    Cardiovascular Disease Laboratory, Department of Pathology, Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba 3058575, Japan
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  • Mingzhe Chen
    Affiliations
    Department of Cardiology, Beijing Third Hospital, Peking University Health Science Center, Beijing 100083, China
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  • Li Chen
    Affiliations
    Institute of Cardiovascular Sciences, Peking University Health Science Center, 38 XueYuan Road, HaiDian District, Beijing 100083, China
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  • Wei Huang
    Correspondence
    Corresponding authors. Institute of Cardiovascular Sciences, Peking University Health Science Center, 38 XueYuan Road, HaiDian District, Beijing 100083, China. Tel.: +86 10 82802769; fax: +86 10 82802769.
    Affiliations
    Institute of Cardiovascular Sciences, Peking University Health Science Center, 38 XueYuan Road, HaiDian District, Beijing 100083, China

    Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Peking University Health Science Center, Beijing 100083, China
    Search for articles by this author
  • George Liu
    Correspondence
    Corresponding authors. Institute of Cardiovascular Sciences, Peking University Health Science Center, 38 XueYuan Road, HaiDian District, Beijing 100083, China. Tel.: +86 10 82802769; fax: +86 10 82802769.
    Affiliations
    Institute of Cardiovascular Sciences, Peking University Health Science Center, 38 XueYuan Road, HaiDian District, Beijing 100083, China

    Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Peking University Health Science Center, Beijing 100083, China
    Search for articles by this author
  • Author Footnotes
    1 These authors contributed equally to this work.

      Abstract

      Recent studies on mice demonstrated that lipoprotein lipase (LPL) located in the arterial wall might play a pro-atherogenic role. There are major differences between humans and mice in lipoprotein metabolism and in susceptibility to atherosclerosis. We have therefore used rabbits fed normal chow diet as a model to assess such localized effects by adenovirus-mediated gene transfer of human catalytically active wild type LPL (hLPLwt) and an inactive mutant (hLPL194) to balloon-injured carotid arteries. By morphometric analysis on cryosections stained with Oil Red O (ORO) we found 7- and 4-fold increases, respectively, of lipid deposition in the arterial walls 7 days after infection with adenovirus expressing hLPLwt or hLPL194, when compared with a virus expressing human alkaline phosphatase (hAP) as control. Macrophages were detected in the arteries expressing both forms of LPL, but apoB was only found in arteries expressing hLPLwt. Expression of the LPL gene products was transient and was gone after 2 weeks, but the accumulated lipid deposits remained between the neointimal and the media layers even after 8 weeks. Our data demonstrate that expression of LPL in the arterial wall (with or without lipase activity) leads to lipid accumulation in balloon-injured rabbit arteries, and could result in enhanced formation of atherosclerotic lesions.

      Keywords

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