Leader(s)

• 

  Rautou Pierre-Emmanuel

  • 0157277731
  • pierre-emmanuel.rautou@inserm.fr

Presentation

Our team is working on the role of vessels in liver disease. We are interested in rare vascular liver diseases (Budd-Chiari syndrome, extrahepatic portal vein thrombosis and porto-sinusoidal vascular disorder), metabolic dysfunction-associated steatohepatitis and cirrhosis.

Current research directions :
– Liver sinusoidal endothelial cells in the progression of liver diseases
– Extracellular vesicles in liver diseases
– Porto-sinusoidal vascular disease

 

Liver sinusoidal endothelial cells in the progression of liver diseases

Recent advances indicate that intestinal and visceral adipose tissues play a key role in liver diseases. This suggests that substances are released by these tissues, influencing liver function. Liver endothelial cells are among the first cells to encounter blood from intestinal and visceral fat tissues. They are an active interface between blood and other hepatic cells. However, the role of liver endothelial cells in liver diseases is paradoxically very poorly understood.

We recently demonstrated that autophagy is defective in liver endothelial cells of patients with Metabolic dysfunction-associated steatohepatitis (MASH) and that this defect is induced by inflammatory mediators present in the portal blood of patients with metabolic syndrome
We also demonstrated that deficiency in autophagy induces liver endothelial cell alterations responsible for liver inflammation, liver cell death and liver fibrosis, thus promoting NASH development (Hammoutene A. J Hepatol. 2019).

Left :Primary murine liver sinusoidal endothelial cells take up acLDL with high efficiency

Right : Liver sinusoidal endothelial cells in murine liver section (green)

Extracellular vesicles in liver diseases

Extracellular vesicles are membrane-bound vesicles released by cells into the extracellular space. They include apoptotic bodies, microvesicles and exosomes : called now large and small vesicles. Extracellular vesicles are able to transmit information from one cell to another. We are currently determining the role of extracellular vesicles in progression and complications of liver diseases. To do so, we analyze their roles in intercellular communication between the liver and other organs, as well as among the liver itself. 

We have recently demonstrated that microvesicles from red blood cells carrying JAK2V671F mutation transfer a protein (myeloperoxidase) to endothelial cells thus increasing arterial response. This data can explain the increase of cardiovascular events in patients with JAK2V617F myeloproliferative neoplasms (Poisson J. J Clin Invest. 2020).

Electronic microscopy view from extracellular vesicles in liver vessels

Extracellular vesicles can also be used as biomarkers. We demonstrated that hepatocyte microvesicles can predict the course of patients with cirrhosis (Bissonnette J. Hepatology. 2017 & Payancé A. Hepatology 2018 & Thietart S. Journal of hepatology. 2020).

In 2023, we have shown that hepatocyte-derived extracellular vesicles are also able to predict liver-related events at 2 years in patients with Child-Pugh class A alcohol-related cirrhosis (Elkrief L. J Hepatol 2023)

Using proteomics on extracellular vesicles, we have identified several new biomarkers that can be used to define sub-populations of extracellular vesicles that could improve the diagnosis of liver diseases.

We are now validating these results in large cohorts of patients: DECISION cohort; PROMICE; RHU QUID NASH.

 

Porto-sinusoidal vascular disorder

Previously called non-cirrhotic portal hypertension or nodular regenerative hyperplasia, is a rare disease characterized by alterations in the portal veins and/or sinusoids leading in some patients to portal hypertension and its complications. We are studying the pathophysiology of this disease as well as the future of patients with this disease. Pr. Pierre-Emmanuel Rautou is responsible of unity of Catheterisme hepatique in Beaujon Hospital.

 

Podcast of Prof PE Rautou on porto-sinusoidal vascular disease: link