Review article| Volume 315, P111-125, December 2020

Transendothelial transport of lipoproteins

  • Erika Jang
    Keenan Centre for Biomedical Research, St. Michael's Hospital, Toronto, Canada

    Department of Laboratory Medicine and Pathobiology, University of Toronto, Canada
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  • Jerome Robert
    Institute of Clinical Chemistry, University of Zurich and University Hospital of Zurich, Switzerland
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  • Lucia Rohrer
    Institute of Clinical Chemistry, University of Zurich and University Hospital of Zurich, Switzerland
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  • Arnold von Eckardstein
    Corresponding author. University Hospital Zurich, Institute of Clinical Chemistry, Raemistrasse 100, CH 8091, ZURICH, Switzerland.
    Institute of Clinical Chemistry, University of Zurich and University Hospital of Zurich, Switzerland
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  • Warren L. Lee
    Corresponding author. Keenan Centre for Biomedical Research, St. Michael's Hospital, 30 Bond St, Toronto, Ontario, Canada.
    Keenan Centre for Biomedical Research, St. Michael's Hospital, Toronto, Canada

    Department of Laboratory Medicine and Pathobiology, University of Toronto, Canada

    Interdepartmental Division of Critical Care, Department of Medicine, University of Toronto, Canada

    Department of Biochemistry, University of Toronto, Canada

    Institute of Medical Science, University of Toronto, Canada
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      • The endothelium limits the entry and exit of lipoproteins into and from the arterial wall, respectively.
      • SR-BI, activin like kinase 1, and caveolin-1 as well as GPER and sphingosine-1-phosphate regulate the transcytosis of LDL.
      • SR-BI, ABCG1, endothelial lipase, the ecto-ATPase/P2Y-receptor axis, VEGF, IL-6/17, and S1P regulate HDL transcytosis.


      The accumulation of low-density lipoproteins (LDL) in the arterial wall plays a pivotal role in the initiation and pathogenesis of atherosclerosis. Conversely, the removal of cholesterol from the intima by cholesterol efflux to high density lipoproteins (HDL) and subsequent reverse cholesterol transport shall confer protection against atherosclerosis. To reach the subendothelial space, both LDL and HDL must cross the intact endothelium. Traditionally, this transit is explained by passive filtration. This dogma has been challenged by the identification of several rate-limiting factors namely scavenger receptor SR-BI, activin like kinase 1, and caveolin-1 for LDL as well as SR-BI, ATP binding cassette transporter G1, and endothelial lipase for HDL. In addition, estradiol, vascular endothelial growth factor, interleukins 6 and 17, purinergic signals, and sphingosine-1-phosphate were found to regulate transendothelial transport of either LDL or HDL. Thorough understanding of transendothelial lipoprotein transport is expected to elucidate new therapeutic targets for the treatment or prevention of atherosclerotic cardiovascular disease and the development of strategies for the local delivery of drugs or diagnostic tracers into diseased tissues including atherosclerotic lesions.

      Graphical abstract


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