title: Hepatic proliferation and angiogenesis markers are increased after portal deprivation in rats: a study of molecular, histological and radiological changes.
abstract: OBJECTIVE
  To determine the pathogenesis of liver nodules, and lesions similar to obliterative portal venopathy, observed after portosystemic shunts or portal vein thrombosis in humans.
  
  
  METHODS
  We conducted an experimental study comparing portacaval shunt (PCS), total portal vein ligation (PVL), and sham (S) operated rats. Each group were either sacrificed at 6 weeks (early) or 6 months (late). Arterial liver perfusion was studied in vivo using CT, and histopathological changes were noted. Liver mRNA levels were quantified by RT-QPCR for markers of inflammation (Il10, Tnfa), proliferation (Il6st, Mki67, Hgf, Hnf4a), angiogenesis: (Vegfa, Vegfr 1, 2 and 3; Pgf), oxidative stress (Nos2, and 3, Hif1a), and fibrosis (Tgfb). PCS and PVL were compared to the S group.
  
  
  RESULTS
  Periportal fibrosis and arterial proliferation was observed in late PCS and PVL groups. CT imaging demonstrated increased arterial liver perfusion in the PCS group. RT-QPCR showed increased inflammatory markers in PCS and PVL early groups. Tnfa and Il10 were increased in PCS and PVL late groups respectively. All proliferative markers increased in the PCS, and Hnf4a in the PVL early groups. Mki67 and Hnf4a were increased in the PCS late group. Nos3 was increased in the early and late PCS groups, and Hif1a was decreased in the PVL groups. Markers of angiogenesis were all increased in the early PCS group, and Vegfr3 and Pgf in the late PCS group. Only Vegfr3 was increased in the PVL groups. Tgf was increased in the PCS groups.
  
  
  CONCLUSIONS
  Portal deprivation in rats induces a sustained increase in intrahepatic markers of inflammation, angiogenesis, proliferation, and fibrosis.
authors.affiliation: Department of Pediatric Surgery, Hôpitaux Universitaires Paris-Sud (Bicêtre), Assistance Publique Hôpitaux de Paris (AP-HP), Université Paris Sud-Paris11, Le Kremlin Bicêtre, France; Institut National de la Santé et de la Recherche Médicale (INSERM): Unité Mixte de Recherche (UMR) 1149, Centre de Recherche sur l'Inflammation, Faculté de Médecine Xavier Bichat, Université Denis Diderot-Paris 7, Paris, France; Laboratoire de Microchirurgie, Agence Générale des Equipements et Produits de Santé (AGEPS), Assistance Publique Hôpitaux de Paris (AP-HP), Paris, France.
authors.forename: Florent
authors.initials: F
authors.lastname: Guérin
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM): Unité Mixte de Recherche (UMR) 1149, Centre de Recherche sur l'Inflammation, Faculté de Médecine Xavier Bichat, Université Denis Diderot-Paris 7, Paris, France; Department of Radiology, Hôpitaux Universitaires Paris Nord Val de Seine (Beaujon), Assistance Publique Hôpitaux de Paris (AP-HP), Université Denis Diderot-Paris 7, Clichy, France.
authors.forename: Mathilde
authors.initials: M
authors.lastname: Wagner
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM): Unité Mixte de Recherche (UMR) 1149, Centre de Recherche sur l'Inflammation, Faculté de Médecine Xavier Bichat, Université Denis Diderot-Paris 7, Paris, France; Laboratoire de Microchirurgie, Agence Générale des Equipements et Produits de Santé (AGEPS), Assistance Publique Hôpitaux de Paris (AP-HP), Paris, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Liné
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM): Unité Mixte de Recherche (UMR) 1149, Centre de Recherche sur l'Inflammation, Faculté de Médecine Xavier Bichat, Université Denis Diderot-Paris 7, Paris, France; Department of Radiology, Hôpitaux Universitaires Paris Nord Val de Seine (Beaujon), Assistance Publique Hôpitaux de Paris (AP-HP), Université Denis Diderot-Paris 7, Clichy, France.
authors.forename: Magaly
authors.initials: M
authors.lastname: Zappa
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM): Unité Mixte de Recherche (UMR) 1149, Centre de Recherche sur l'Inflammation, Faculté de Médecine Xavier Bichat, Université Denis Diderot-Paris 7, Paris, France.
authors.forename: Magali
authors.initials: M
authors.lastname: Fasseu
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM): Unité Mixte de Recherche (UMR) 1149, Centre de Recherche sur l'Inflammation, Faculté de Médecine Xavier Bichat, Université Denis Diderot-Paris 7, Paris, France; Department of Pathology, Hôpitaux Universitaires Paris-Nord-Val-de-Seine (Beaujon), Assistance Publique Hôpitaux de Paris (AP-HP), Université Denis Diderot-Paris 7, Clichy, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Paradis
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM): Unité Mixte de Recherche (UMR) 1149, Centre de Recherche sur l'Inflammation, Faculté de Médecine Xavier Bichat, Université Denis Diderot-Paris 7, Paris, France; Department of Radiology, Hôpitaux Universitaires Paris Nord Val de Seine (Beaujon), Assistance Publique Hôpitaux de Paris (AP-HP), Université Denis Diderot-Paris 7, Clichy, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Vilgrain
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM): Unité Mixte de Recherche (UMR) 1149, Centre de Recherche sur l'Inflammation, Faculté de Médecine Xavier Bichat, Université Denis Diderot-Paris 7, Paris, France; Department of Radiology, Hôpitaux Universitaires Paris Nord Val de Seine (Beaujon), Assistance Publique Hôpitaux de Paris (AP-HP), Université Denis Diderot-Paris 7, Clichy, France.
authors.forename: Bernard E
authors.initials: BE
authors.lastname: Van Beers
authors.affiliation: Laboratoire de Microchirurgie, Agence Générale des Equipements et Produits de Santé (AGEPS), Assistance Publique Hôpitaux de Paris (AP-HP), Paris, France.
authors.forename: Josette
authors.initials: J
authors.lastname: Legagneux
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM): Unité Mixte de Recherche (UMR) 1149, Centre de Recherche sur l'Inflammation, Faculté de Médecine Xavier Bichat, Université Denis Diderot-Paris 7, Paris, France; Department of Hepatology, Hôpitaux Universitaires Paris-Nord-Val-de-Seine (Beaujon), Assistance Publique Hôpitaux de Paris (AP-HP), Université Denis Diderot-Paris 7, Clichy, France.
authors.forename: Richard
authors.initials: R
authors.lastname: Moreau
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM): Unité Mixte de Recherche (UMR) 1149, Centre de Recherche sur l'Inflammation, Faculté de Médecine Xavier Bichat, Université Denis Diderot-Paris 7, Paris, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Lettéron
mesh_terms: D000818:Animals; D006502:Budd-Chiari Syndrome / Q000235:genetics* / Q000473:pathology*; D049109:Cell Proliferation; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D005819:Genetic Markers / Q000235:genetics*; D007249:Inflammation / Q000235:genetics; D008099:Liver / Q000098:blood supply / Q000000981:diagnostic imaging* / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000235:genetics; D018384:Oxidative Stress; D011169:Portal Vein / Q000601:surgery*; D011859:Radiography; D051381:Rats
chemical_list: D005819:Genetic Markers