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Resolution of liver fibrosis requires myeloid cell-driven sinusoidal angiogenesis.
Kantari-Mimoun, Chahrazade; Castells, Magali; Klose, Ralph; Meinecke, Anna-Katharina; Lemberger, Ursula J; Rautou, Pierre-Emmanuel; Pinot-Roussel, Hélène; Badoual, Cécile; Schrödter, Katrin; Österreicher, Christoph H; Fandrey, Joachim; Stockmann, Christian.
Afiliación
  • Kantari-Mimoun C; Institut National de la Santé et de la Recherche Médicale (INSERM), Unit 970, Paris Cardiovascular Research Center, Paris, France.
  • Castells M; Institut National de la Santé et de la Recherche Médicale (INSERM), Unit 970, Paris Cardiovascular Research Center, Paris, France.
  • Klose R; Institut National de la Santé et de la Recherche Médicale (INSERM), Unit 970, Paris Cardiovascular Research Center, Paris, France.
  • Meinecke AK; Institut für Physiologie, Universitätsklinikum Essen, Universität Duisburg-Essen, Duisburg, Germany.
  • Lemberger UJ; Institute of Pharmacology, Center for Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria.
  • Rautou PE; Institut National de la Santé et de la Recherche Médicale (INSERM), Unit 970, Paris Cardiovascular Research Center, Paris, France.
  • Pinot-Roussel H; DHU Unity, Pôle des Maladies de l'Appareil Digestif, Service d'Hépatologie, Centre de Référence des Maladies Vasculaires du Foie, Hôpital Beaujon, AP-HP, Clichy, France.
  • Badoual C; Institut National de la Santé et de la Recherche Médicale (INSERM), Unit 970, Paris Cardiovascular Research Center, Paris, France.
  • Schrödter K; Service d'Anatomie et Pathologie, Hôpital Européen Georges Pompidou, APHP, Paris, France.
  • Österreicher CH; Institut National de la Santé et de la Recherche Médicale (INSERM), Unit 970, Paris Cardiovascular Research Center, Paris, France.
  • Fandrey J; Service d'Anatomie et Pathologie, Hôpital Européen Georges Pompidou, APHP, Paris, France.
  • Stockmann C; Institut für Physiologie, Universitätsklinikum Essen, Universität Duisburg-Essen, Duisburg, Germany.
Hepatology ; 61(6): 2042-55, 2015 Jun.
Article en En | MEDLINE | ID: mdl-25475053
UNLABELLED: Angiogenesis is a key feature of liver fibrosis. Although sinusoidal remodeling is believed to contribute to fibrogenesis, the impact of sinusoidal angiogenesis on the resolution of liver fibrosis remains undefined. Myeloid cells, particularly macrophages, constantly infiltrate the fibrotic liver and can profoundly contribute to remodeling of liver sinusoids. We observe that the development of fibrosis is associated with decreased hepatic vascular endothelial growth factor (VEGF) expression as well as sinusoidal rarefication of the fibrotic scar. In contrast, the resolution of fibrosis is characterized by a rise in hepatic VEGF levels and revascularization of the fibrotic tissue. Genetic ablation of VEGF in myeloid cells or pharmacological inhibition of VEGF receptor 2 signaling prevents this angiogenic response and the resolution of liver fibrosis. We observe increased expression of matrix metalloproteases as well as decreased expression of tissue inhibitor of metalloproteases confined to sinusoidal endothelial cells in response to myeloid cell VEGF. Remarkably, reintroduction of myeloid cell-derived VEGF upon recovery restores collagenolytic acitivity and the resolution of fibrosis. CONCLUSION: We identify myeloid cell-derived VEGF as a critical regulator of extracellular matrix degradation by liver endothelial cells, thereby unmasking an unanticipated link between angiogenesis and the resolution of fibrosis.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neovascularización Fisiológica / Células Mieloides / Hígado / Cirrosis Hepática Tipo de estudio: Prognostic_studies Límite: Animals / Female / Humans / Male Idioma: En Revista: Hepatology Año: 2015 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Estados Unidos
Texto completo
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XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neovascularización Fisiológica / Células Mieloides / Hígado / Cirrosis Hepática Tipo de estudio: Prognostic_studies Límite: Animals / Female / Humans / Male Idioma: En Revista: Hepatology Año: 2015 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Estados Unidos