There is no unique specific marker of LSECs, apart from their fenestrae devoid of diaphragm in the absence of basement membrane. A combination of markers is thus mandatory for their identification.
ReviewLiver sinusoidal endothelial cells: Physiology and role in liver diseases
Introduction
The vascular endothelium, representing the interface between blood and other tissues, is not only a physical barrier, but contributes to different physiological and pathological processes, including hemostasis/thrombosis, metabolites transportation, inflammation, angiogenesis and vascular tone [1]. Liver sinusoidal endothelial cells (LSECs) form the wall of the liver sinusoids and represent approximately 15 to 20% of liver cells but only 3% of the total liver volume [2]. LSECs are highly specialized endothelial cells. They have a discontinuous architecture meaning that fusion of the luminal and abluminal plasma membrane occurs at other sites than cell junctions, in areas called ‘fenestrae’. This review focuses on the role of LSECs in physiological conditions and their involvement in liver diseases.
Section snippets
Formation of sinusoids during embryogenesis
As illustrated in Fig. 1, an early structural differentiation of hepatic sinusoids occurs between gestational weeks 5 and 12 in human embryos [3]. During that period, LSECs gradually loose cell markers of continuous endothelial cells including platelet endothelial adhesion molecule-1 (PECAM-1, also called cluster of differentiation (CD)31), CD34 and 1F10 antigen, and acquire markers of adult sinusoidal cells including CD4, CD32 and the intracellular adhesion molecule-1 (ICAM-1). This
Markers of LSEC
Identification and isolation of LSECs is a major challenge for the understanding of liver physiology and diseases. However, technical barriers as well as a lack of consensual specific LSEC markers explain that LSECs populations differ between research groups, which limits the interpretation and the
Chronic liver diseases
LSECs play a key role in chronic liver disease initiation and progression, through four processes: sinusoid capillarization, angiogenesis, angiocrine signals and vasoconstriction. The loss of the specific phenotype of LSECs, including the disappearance of the fenestrae, the development of a basement membrane, and the appearance of specific markers is called capillarization and is an early even in chronic liver injury. When capillarized, LSECs lose their capacity to inactivate hepatic stellate
Conclusion
In conclusion, LSECs have a unique highly permeable phenotype allowing the passage of certain but not all molecules and cells. They also have a very special localization at the interface between blood cells on the one side and hepatocytes and hepatic stellate cells on the other side. LSECs are in constant interaction with other liver cells [83]. LSECs are implicated in most liver diseases including chronic liver disease initiation and progression, hepatocellular carcinoma development and
Financial support
This work was supported by the Agence Nationale pour la Recherche (ANR-14-CE12-0011 and ANR-14-CE35-0022) and by the Association Francaise pour l’Etude du foie (AFEF 2014) and J.P by the “poste d’accueil INSERM”.
Conflict of interest
The authors declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.
Authors’ contributions
JP, SL and PER drafted the manuscript. FD, CMB, RM and DV discussed and critically revised the manuscript.
Acknowledgments
We thank Servier medical art for providing some images included in the figures.
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These authors contributed equally as joint first authors.