Liver sinusoidal endothelial cells (LSECs) function and NAFLD; NO-based therapy targeted to the liver.

Liver sinusoidal endothelial cells (LSECs) present unique, highly specialised endothelial cells in the body. Unlike the structure and function of typical, vascular endothelial cells, LSECs are comprised of fenestrations, display high endocytic capacity and play a prominent role in maintaining overall liver homeostasis. LSEC dysfunction has been regarded as a key event in multiple liver disorders; however, its role and diagnostic, prognostic and therapeutic significance in nonalcoholic fatty liver disease (NAFLD) is still neglected. The purpose of this review is to provide an overview of the importance of LSECs in NAFLD. Attention is focused on the LSECs-mediated NO-dependent mechanisms in NAFLD development. We briefly describe the unique, highly specialised phenotype of LSECs and consequences of LSEC dysfunction on function of hepatic stellate cells (HSC) and hepatocytes. The potential efficacy of liver selective NO donors against liver steatosis and novel treatment approaches to modulate LSECs-driven liver pathology including NAFLD are also highlighted.