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Liver endothelial cells in NAFLD and transition to NASH and HCC

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Abstract

Non-alcoholic fatty liver disease (NAFLD) is considered as the hepatic manifestation of metabolic syndrome, which is characterised by obesity, insulin resistance, hypercholesterolemia and hypertension. NAFLD is the most frequent liver disease worldwide and more than 10% of NAFLD patients progress to the inflammatory and fibrotic stage of non-alcoholic steatohepatitis (NASH), which can lead to end-stage liver disease including hepatocellular carcinoma (HCC), the most frequent primary malignant liver tumor. Liver sinusoidal endothelial cells (LSEC) are strategically positioned at the interface between blood and hepatic parenchyma. LSECs are highly specialized cells, characterised by the presence of transcellular pores, called fenestrae, and exhibit anti-inflammatory and anti-fibrotic characteristics under physiological conditions. However, during NAFLD development they undergo capillarisation and acquire a phenotype similar to vascular endothelial cells, actively promoting all pathophysiological aspects of NAFLD, including steatosis, inflammation, and fibrosis. LSEC dysfunction is critical for the progression to NASH and HCC while restoring LSEC homeostasis appears to be a promising approach to prevent NAFLD progression and its complications and even reverse tissue damage. In this review we present current information on the role of LSEC throughout the progressive phases of NAFLD, summarising in vitro and in vivo experimental evidence and data from human studies.

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Funding

Supported by the Hellenic Foundation for Research and Innovation (HFRI #3222 to AC).

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  1. Nikolaos I. Vlachogiannis and Antonios Chatzigeorgiou contributed equally as senior authors.

Authors and Affiliations

  1. Department of Physiology, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias Str., 11527, Athens, Greece

    Rallia-Iliana Velliou, Aigli-Ioanna Legaki, Polyxeni Nikolakopoulou, Nikolaos I. Vlachogiannis & Antonios Chatzigeorgiou

  2. Institute for Clinical Chemistry and Laboratory Medicine, University Hospital and Faculty of Medicine Carl Gustav Carus of TU Dresden, Fetscherstrasse 74, 01307, Dresden, Germany

    Antonios Chatzigeorgiou

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  1. Rallia-Iliana Velliou
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Velliou, RI., Legaki, AI., Nikolakopoulou, P. et al. Liver endothelial cells in NAFLD and transition to NASH and HCC. Cell. Mol. Life Sci. 80, 314 (2023). https://doi.org/10.1007/s00018-023-04966-7

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