Pierre-Emmanuel RAUTOU - Université Paris-Cité

Abstract

Non-alcoholic fatty liver disease (NAFLD) and its complications are an expanding health problem associated with the metabolic syndrome. Liver sinusoidal endothelial cells (LSECs) are highly specialized endothelial cells localized at the interface between the blood derived from the gut and the adipose tissue on the one side, and other liver cells on the other side. In physiological conditions, LSECs are gatekeepers of liver homeostasis. LSECs display anti-inflammatory and anti-fibrogenic properties by preventing Kupffer cell and hepatic stellate cell activation and regulating intrahepatic vascular resistance and portal pressure. This presentation will focus on changes occurring in LSECs in NAFLD and on their consequences on NAFLD progression and complications. Capillarization, namely the loss of LSEC fenestrae, and LSEC dysfunction, namely the loss of the ability of LSECs to generate vasodilator agents in response to increased shear stress both occur early in NAFLD. These LSEC changes favour steatosis development and set the stage for NAFLD progression. At the stage of non-alcoholic steatohepatitis, altered LSECs release inflammatory mediators and contribute to the recruitment of inflammatory cells, thus promoting liver injury and inflammation. Altered LSECs also fail to maintain hepatic stellate cell quiescence and release fibrogenic mediators, including Hedgehog signalling molecules, promoting liver fibrosis. Liver angiogenesis is increased in NAFLD and contributes to liver inflammation and fibrosis, but also to hepatocellular carcinoma development. Thus, improving LSEC health appears to be a promising approach to prevent NAFLD progression and complications.
 

Biography

Pierre-Emmanuel Rautou (MD, PhD)  is a clinical specialist in Hepatology with a PhD in vascular biology (2011). He is Professor of Hepatology at Université Paris-Cité and Hôpital Beaujon (Clichy, France) since 2016. He is the head of the splanchnic hemodynamic laboratory at Beaujon Hospital (Clichy, France) since 2012. He is also leading an Inserm team dedicated to the study of the role of vessels in liver diseases, at the INSERM Unit 1149 (Paris Research Center on Inflammation).