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  • Review Article
  • Published:

The emerging roles of microvesicles in liver diseases

Nature Reviews Gastroenterology & Hepatology volume 11, pages 350–361 (2014)Cite this article

Subjects

Key Points

  • Microvesicles (MVs) are 0.1–1.0 μm vesicles containing lipids, proteins, RNAs and microRNAs; they are formed by budding from the cellular plasma membrane

  • Circulating levels of several subpopulations of MVs are increased in patients with liver diseases, probably due to enhanced MV production and decreased MV clearance, related to the individual liver disorder

  • MVs are now implicated at many stages of liver disease progression, including liver fibrogenesis, portal hypertension and activation of coagulation

  • Several results suggest that MVs have a role in hepatocellular carcinoma by conveying information between tumour cells and between tumour and neighbouring cells

  • High levels of circulating procoagulant MVs have been found in patients with acute liver failure and might contribute to normal or hypercoagulable global haemostasis in this setting

  • MVs have promise as diagnostic and prognostic biomarkers in patients with liver diseases

Abstract

Microvesicles (MVs) are extracellular vesicles released by virtually all cells, under both physiological and pathological conditions. They contain lipids, proteins, RNAs and microRNAs and act as vectors of information that regulate the function of target cells. This Review provides an overview of the studies assessing circulating MV levels in patients with liver diseases, together with an insight into the mechanisms that could account for these changes. We also present a detailed analysis of the implication of MVs in key processes of liver diseases. MVs have a dual role in fibrosis as certain types of MVs promote fibrolysis by increasing expression of matrix metalloproteinases, whereas others promote fibrosis by stimulating processes such as angiogenesis. MVs probably enhance portal hypertension by contributing to intrahepatic vasoconstriction, splanchnic vasodilation and angiogenesis. As MVs can modulate vascular permeability, vascular tone and angiogenesis, they might contribute to several complications of cirrhosis including hepatic encephalopathy, hepatopulmonary syndrome and hepatorenal syndrome. Several results also suggest that MVs have a role in hepatocellular carcinoma. Although MVs represent promising biomarkers in patients with liver disease, methods of isolation and subsequent analysis must be standardized.

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Figure 1: Definitions of microvesicles.
Figure 2: Microvesicles in liver diseases.
Figure 3: Microvesicles in liver fibrosis.
Figure 4: Microvesicles in portal hypertension.
Figure 5: Microvesicles in hepatocellular carcinoma.

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Acknowledgements

This authors of this Review receive funding for laboratory research from the Société Nationale Française de Gastroentérologie (SNFGE), the Association Française pour l'Étude du Foie (AFEF) and the Agence Nationale pour la Recherche (ANR-12-EMMA-0012-03).

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  1. INSERM, UMRS 938, Centre de Recherche Saint-Antoine, Sorbonne Universités, Université Pierre et Marie Curie Paris 6, 27 Rue Chaligny, Paris, 75571, France

    Sara Lemoinne, Dominique Thabut & Chantal Housset

  2. INSERM, U773, Centre de Recherche Biomédicale Bichat-Beaujon CRB3, Université Paris-Diderot-Paris 7, Hôpital Bichat, 46 Rue Henri Huchard, Paris, 75018, France

    Richard Moreau

  3. Service d'hépatologie, Hôpital Beaujon, 100 Boulevard du Général Leclerc, Clichy, 92100, France

    Dominique Valla

  4. INSERM, U970, Paris Cardiovascular Research Center, Paris, Université Paris Descartes, Sorbonne Paris Cité, 56 Rue Leblanc, Paris, 75015, France

    Chantal M. Boulanger & Pierre-Emmanuel Rautou

Authors
  1. Sara Lemoinne
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  2. Dominique Thabut
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  3. Chantal Housset
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  4. Richard Moreau
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  5. Dominique Valla
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  6. Chantal M. Boulanger
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  7. Pierre-Emmanuel Rautou
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Contributions

S. Lemoinne and P.-E. Rautou contributed to all aspects of the preparation of this manuscript. D. Thabut, C. Housset, R. Moreau, D. Valla and C. M. Boulanger contributed to discussion of content and reviewing/editing the manuscript before submission.

Corresponding author

Correspondence to Pierre-Emmanuel Rautou.

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The authors declare no competing financial interests.

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Lemoinne, S., Thabut, D., Housset, C. et al. The emerging roles of microvesicles in liver diseases. Nat Rev Gastroenterol Hepatol 11, 350–361 (2014). https://doi.org/10.1038/nrgastro.2014.7

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