New aspects of hepatic endothelial cells in physiology and nonalcoholic fatty liver disease

Am J Physiol Cell Physiol. 2020 Jun 1;318(6):C1200-C1213. doi: 10.1152/ajpcell.00062.2020. Epub 2020 May 6.

Abstract

The liver is the central metabolic hub for carbohydrate, lipid, and protein metabolism. It is composed of four major types of cells, including hepatocytes, endothelial cells (ECs), Kupffer cells, and stellate cells. Hepatic ECs are highly heterogeneous in both mice and humans, representing the second largest population of cells in liver. The majority of them line hepatic sinusoids known as liver sinusoidal ECs (LSECs). The structure and biology of LSECs and their roles in physiology and liver disease were reviewed recently. Here, we do not give a comprehensive review of LSEC structure, function, or pathophysiology. Instead, we focus on the recent progress in LSEC research and other hepatic ECs in physiology and nonalcoholic fatty liver disease and other hepatic fibrosis-related conditions. We discuss several current areas of interest, including capillarization, scavenger function, autophagy, cellular senescence, paracrine effects, and mechanotransduction. In addition, we summarize the strengths and weaknesses of evidence for the potential role of endothelial-to-mesenchymal transition in liver fibrosis.

Keywords: LSECs; NAFLD; autophagy; cellular senescence; fibrosis; hepatic endothelium; scavenger function.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Autophagy
  • Capillaries / metabolism*
  • Capillaries / pathology
  • Cell Differentiation
  • Cell Proliferation
  • Cellular Senescence
  • Endothelial Cells / metabolism*
  • Endothelial Cells / pathology
  • Epithelial-Mesenchymal Transition
  • Humans
  • Inflammation Mediators / metabolism
  • Liver / blood supply*
  • Liver Cirrhosis / metabolism*
  • Liver Cirrhosis / pathology
  • Mechanotransduction, Cellular
  • Non-alcoholic Fatty Liver Disease / metabolism*
  • Non-alcoholic Fatty Liver Disease / pathology
  • Paracrine Communication
  • Reactive Oxygen Species / metabolism

Substances

  • Inflammation Mediators
  • Reactive Oxygen Species