Vessels in liver diseases (Atip-Avenir)
Department Hepato-Gastroenterology Department
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
Publication date : 09 June 2023 More
Hepatocyte-derived biomarkers predict liver-related events at 2 years in Child-Pugh class A alcohol-related cirrhosis
Authors : Elkrief Laure Nathalie Ganne-Carrié Manceau Hana Tanguy Marion Shantha Ram Valainathan Alix Riescher-Tuczkiewicz Biquard Louise Nathalie Barget Cendrine Chaffaut Alexandre Louvet Paradis Valérie Marianne Ziol Rikke Bæk Malene Møller Jørgensen Guillaume Van Niel Pierre-Michael Coly Hammoutene Adel Fanny Dujardin Katell Peoc'h Thierry Poynard Sylvie Chevret Rautou Pierre-Emmanuel CIRRAL group
Publication date : 01 December 2020 More
Extracellular vesicles as biomarkers in liver diseases: A clinician’s point of view
Authors : Thietart Sara Rautou Pierre-Emmanuel
Publication date : 01 March 2020 More
A defect in endothelial autophagy occurs in patients with non-alcoholic steatohepatitis and promotes inflammation and fibrosis
Authors : Hammoutene Adel Biquard Louise Juliette Lasselin Marouane Kheloufi Tanguy Marion Anne-Clémence Vion Jules Mérian Nathalie Colnot Xavier Loyer Alain Tedgui Patrice Codogno Lotersztajn Sophie Paradis Valérie Chantal M Boulanger Rautou Pierre-Emmanuel
Publication date : 01 June 2019 More
Role of liver sinusoidal endothelial cells in non-alcoholic fatty liver disease.
Authors : Hammoutene Adel Rautou Pierre-Emmanuel
Publication date : 01 October 2018 More
Hepatocyte microvesicle levels improve prediction of mortality in patients with cirrhosis.
Authors : Payancé A Silva-Junior G Bissonnette J Tanguy Marion Pasquet B Levi C Roux O Nekachtali O Baiges A Hernández-Gea V Laouénan C Lebrec D ALBUQUERQUE Miguel Paradis Valérie Moreau Richard Valla Dominique Durand François Boulanger CM Garcia-Pagan JC Rautou Pierre-Emmanuel
Publication date : 01 August 2017 More
A prospective study of the utility of plasma biomarkers to diagnose alcoholic hepatitis.
Authors : Bissonnette J Altamirano J Devue C Roux O Payancé A Lebrec D Bedossa Pierre Valla Dominique Durand François Ait-Oufella H Sancho-Bru P Caballeria J Ginès P Boulanger CM Bataller R Rautou Pierre-Emmanuel
Publication date : 04 January 2017 More
Liver sinusoidal endothelial cells: physiology and role in liver diseases
Authors : Poisson Johanne Lemoinne S Boulanger C Durand François Moreau Richard Valla Dominique Rautou Pierre-Emmanuel
Publication date : 15 January 2016 More
Hepatocyte Tissue Factor Contributes to the Hypercoagulable State in a Mouse Model of Chronic Liver Injury.
Authors : Rautou Pierre-Emmanuel Tatsumi K Antoniak S Owens AP Sparkenbaugh E Holle LA Wolberg AS Kopec AK Pawlinski R Luyendyk JP Mackman N Poisson Johanne Lemoinne S Boulanger C Durand François Moreau Richard Valla Dominique Rautou Pierre-Emmanuel
Publication date : 14 June 2014 More
The emerging roles of microvesicles in liver diseases.
Nat Rev Gastro Hepat
Authors : Lemoinne S Thabut D Housset C Moreau Richard Valla Dominique Boulanger CM Rautou Pierre-Emmanuel
Publication date : 30 March 2012 More
Abnormal Plasma Microparticles Impair Vasoconstrictor Responses in Patients with Cirrhosis.
Authors : Rautou Pierre-Emmanuel Bresson J Sainte-Marie Y Vion AC Paradis Valérie Renard JM Devue C Heymes C Letteron Philippe Elkrief Laure Lebrec D Valla Dominique Tedgui A Moreau Richard Boulanger CM