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Liver sinusoidal endothelial cells: Physiology and role in liver diseases

  • Author Footnotes
    † These authors contributed equally as joint first authors.
    Johanne Poisson
    Footnotes
    † These authors contributed equally as joint first authors.
    Affiliations
    INSERM, UMR-970, Paris Cardiovascular Research Center – PARCC, Paris, France

    Université Paris Descartes, Sorbonne Paris Cité, Paris, France
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  • Author Footnotes
    † These authors contributed equally as joint first authors.
    Sara Lemoinne
    Footnotes
    † These authors contributed equally as joint first authors.
    Affiliations
    INSERM, UMRS 938, Centre de Recherche Saint-Antoine, Université Pierre et Marie Curie Paris 6, Paris, France

    Service d’hépatologie, Hôpital Saint-Antoine, APHP, Paris, France
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  • Chantal Boulanger
    Affiliations
    INSERM, UMR-970, Paris Cardiovascular Research Center – PARCC, Paris, France

    Université Paris Descartes, Sorbonne Paris Cité, Paris, France
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  • François Durand
    Affiliations
    Service d’hépatologie, DHU Unity Hôpital Beaujon, APHP, Clichy, France

    INSERM, UMR-1149, Centre de Recherche sur l’inflammation, Paris-Clichy, France

    Université Denis Diderot-Paris 7, Sorbonne Paris Cité, 75018 Paris, France
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  • Richard Moreau
    Affiliations
    Service d’hépatologie, DHU Unity Hôpital Beaujon, APHP, Clichy, France

    INSERM, UMR-1149, Centre de Recherche sur l’inflammation, Paris-Clichy, France

    Université Denis Diderot-Paris 7, Sorbonne Paris Cité, 75018 Paris, France
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  • Dominique Valla
    Affiliations
    Service d’hépatologie, DHU Unity Hôpital Beaujon, APHP, Clichy, France

    INSERM, UMR-1149, Centre de Recherche sur l’inflammation, Paris-Clichy, France

    Université Denis Diderot-Paris 7, Sorbonne Paris Cité, 75018 Paris, France
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  • Pierre-Emmanuel Rautou
    Correspondence
    Corresponding author. Address: Service d’Hépatologie, Hôpital Beaujon, 100 Boulevard du Général Leclerc, 92110 Clichy, France. Tel.: +33 1 40 87 52 83; fax: +33 1 40 87 54 87.
    Affiliations
    INSERM, UMR-970, Paris Cardiovascular Research Center – PARCC, Paris, France

    Université Paris Descartes, Sorbonne Paris Cité, Paris, France

    Service d’hépatologie, DHU Unity Hôpital Beaujon, APHP, Clichy, France

    INSERM, UMR-1149, Centre de Recherche sur l’inflammation, Paris-Clichy, France

    Université Denis Diderot-Paris 7, Sorbonne Paris Cité, 75018 Paris, France
    Search for articles by this author
  • Author Footnotes
    † These authors contributed equally as joint first authors.

      Summary

      Liver sinusoidal endothelial cells (LSECs) are highly specialized endothelial cells representing the interface between blood cells on the one side and hepatocytes and hepatic stellate cells on the other side. LSECs represent a permeable barrier. Indeed, the association of ‘fenestrae’, absence of diaphragm and lack of basement membrane make them the most permeable endothelial cells of the mammalian body. They also have the highest endocytosis capacity of human cells. In physiological conditions, LSECs regulate hepatic vascular tone contributing to the maintenance of a low portal pressure despite the major changes in hepatic blood flow occurring during digestion. LSECs maintain hepatic stellate cell quiescence, thus inhibiting intrahepatic vasoconstriction and fibrosis development. In pathological conditions, LSECs play a key role in the initiation and progression of chronic liver diseases. Indeed, they become capillarized and lose their protective properties, and they promote angiogenesis and vasoconstriction. LSECs are implicated in liver regeneration following acute liver injury or partial hepatectomy since they renew from LSECs and/or LSEC progenitors, they sense changes in shear stress resulting from surgery, and they interact with platelets and inflammatory cells. LSECs also play a role in hepatocellular carcinoma development and progression, in ageing, and in liver lesions related to inflammation and infection. This review also presents a detailed analysis of the technical aspects relevant for LSEC analysis including the markers these cells express, the available cell lines and the transgenic mouse models. Finally, this review provides an overview of the strategies available for a specific targeting of LSECs.

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