Open AccessSinusoidal endotheliopathy in nonalcoholic steatohepatitis: therapeutic implications
Author(s) -
Samar H. Ibrahim
Publication year - 2021
Publication title -
american journal of physiology. gastrointestinal and liver physiology/american journal of physiology: gastrointestinal and liver physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.644
H-Index - 169
eISSN - 1522-1547
pISSN - 0193-1857
DOI - 10.1152/ajpgi.00009.2021
Subject(s) - nonalcoholic fatty liver disease , chemokine , immune system , biology , inflammation , cell adhesion , immunology , microbiology and biotechnology , cell adhesion molecule , medicine , cell , fatty liver , pathology , disease , biochemistry
Liver sinusoidal endothelial cells (LSECs) are distinct subtypes of endothelial cells lining a low flow vascular bed at the interface of the liver parenchyma and the circulating immune cells and soluble factors. Emerging literature implicates LSEC in the pathogenesis and progression of nonalcoholic fatty liver disease (NAFLD). During the evolution of NAFLD, LSEC dysfunction ensues. LSECs undergo morphological and functional transformation known as "capillarization," as well as a pathogenic increase in surface adhesion molecules expression, referred to in this review as "endotheliopathy." LSECs govern the composition of hepatic immune cell populations in nonalcoholic steatohepatis (NASH) by mediating leukocyte subset adhesion through specific combinations of activated adhesion molecules and secreted chemokines. Moreover, extracellular vesicles released by hepatocyte under lipotoxic stress in NASH act as a catalyst for the inflammatory response and promote immune cell chemotaxis and adhesion. In the current review, we highlight leukocyte adhesion to LSEC as an initiating event in the sterile inflammatory response in NASH. We discuss preclinical studies targeting immune cells adhesion in NASH mouse models and potential therapeutic anti-inflammatory strategies for human NASH.