TY - JOUR
T1 - Sinusoidal endotheliopathy in nonalcoholic steatohepatitis
T2 - Therapeutic implications
AU - Ibrahim, Samar H.
N1 - Funding Information:
Research reported in this publication was supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health (NIH) under Award DK 122948 (to S. H. Ibrahim), the NIH Silvio O. Conte Digestive Diseases Research Core Centers P30 grant mechanism (DK084567), and the Mayo Clinic.
Publisher Copyright:
© 2021 the American Physiological Society.
PY - 2021/7
Y1 - 2021/7
N2 - 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.
AB - 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.
KW - Adhesion
KW - Inflammation
KW - Liver sinusoidal endothelial cells
KW - Nonalcoholic steatohepatitis
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U2 - 10.1152/AJPGI.00009.2021
DO - 10.1152/AJPGI.00009.2021
M3 - Review article
C2 - 34037463
AN - SCOPUS:85109739103
VL - 321
SP - G67-G74
JO - American Journal of Physiology - Renal Fluid and Electrolyte Physiology
JF - American Journal of Physiology - Renal Fluid and Electrolyte Physiology
SN - 1931-857X
IS - 1
ER -