title: Immunomodulatory and antioxidant function of albumin stabilises the endothelium and improves survival in a rodent model of chronic liver failure.
abstract: OBJECTIVE
  Liver failure is characterized by endothelial dysfunction, which results in hemodynamic disturbances leading to renal failure. Albumin infusion improves hemodynamics and prevents renal dysfunction in advance liver failure. These effects are only partly explained by the oncotic properties of albumin. This study was designed to test the hypothesis that albumin exerts its beneficial effects by stabilising endothelial function.
  
  
  METHODS
  In vivo: systemic hemodynamics, renal function, markers of endothelial dysfunction (ADMA) and inflammation were studied in analbuminaemic and Sprague-Dawley rats, 6-weeks after sham/bile duct ligation surgery. In vitro: human umbilical vein endothelial cells were stimulated with LPS with or without albumin. We studied protein expression and gene expression of adhesion molecules, intracellular reactive oxygen species, and cell stress markers.
  
  
  RESULTS
  Compared to controls, analbuminaemic rats had significantly greater hemodynamic deterioration after bile duct ligation, resulting in worse renal function and shorter survival. This was associated with significantly greater plasma renin activity, worse endothelial function, and disturbed inflammatory response. In vitro studies showed that albumin was actively taken up by endothelial cells. Incubation of albumin pre-treated endothelial cells with LPS was associated with significantly less activation compared with untreated cells, decreased intracellular reactive oxygen species, and markers of cell stress.
  
  
  CONCLUSIONS
  These results show, for the first time, that absence of albumin is characterised by worse systemic hemodynamics, renal function and higher mortality in a rodent model of chronic liver failure and illustrates the important non-oncotic properties of albumin in protecting against endothelial dysfunction.
authors.affiliation: Liver Failure Group, UCL Institute for Liver and Digestive Health, The Royal Free Hospital, Pond Street, London NW3 2PF, United Kingdom.
authors.forename: Rita
authors.initials: R
authors.lastname: Garcia-Martinez
authors.affiliation: Liver Failure Group, UCL Institute for Liver and Digestive Health, The Royal Free Hospital, Pond Street, London NW3 2PF, United Kingdom.
authors.forename: Fausto
authors.initials: F
authors.lastname: Andreola
authors.affiliation: Liver Failure Group, UCL Institute for Liver and Digestive Health, The Royal Free Hospital, Pond Street, London NW3 2PF, United Kingdom.
authors.forename: Gautam
authors.initials: G
authors.lastname: Mehta
authors.affiliation: Division of Medicine, University College London, London, United Kingdom.
authors.forename: Katie
authors.initials: K
authors.lastname: Poulton
authors.affiliation: Liver Failure Group, UCL Institute for Liver and Digestive Health, The Royal Free Hospital, Pond Street, London NW3 2PF, United Kingdom.
authors.forename: Marc
authors.initials: M
authors.lastname: Oria
authors.affiliation: Liver Failure Group, UCL Institute for Liver and Digestive Health, The Royal Free Hospital, Pond Street, London NW3 2PF, United Kingdom.
authors.forename: Maria
authors.initials: M
authors.lastname: Jover
authors.affiliation: Center for Hepatology, UCL Institute for Liver and Digestive Health, The Royal Free Hospital, Pond Street, London NW3 2PF, United Kingdom.
authors.forename: Junpei
authors.initials: J
authors.lastname: Soeda
authors.affiliation: Liver Failure Group, UCL Institute for Liver and Digestive Health, The Royal Free Hospital, Pond Street, London NW3 2PF, United Kingdom.
authors.forename: Jane
authors.initials: J
authors.lastname: Macnaughtan
authors.affiliation: Liver Failure Group, UCL Institute for Liver and Digestive Health, The Royal Free Hospital, Pond Street, London NW3 2PF, United Kingdom.
authors.forename: Francesco
authors.initials: F
authors.lastname: De Chiara
authors.affiliation: Liver Failure Group, UCL Institute for Liver and Digestive Health, The Royal Free Hospital, Pond Street, London NW3 2PF, United Kingdom.
authors.forename: Abeba
authors.initials: A
authors.lastname: Habtesion
authors.affiliation: Liver Failure Group, UCL Institute for Liver and Digestive Health, The Royal Free Hospital, Pond Street, London NW3 2PF, United Kingdom.
authors.forename: Rajeshwar P
authors.initials: RP
authors.lastname: Mookerjee
authors.affiliation: Liver Failure Group, UCL Institute for Liver and Digestive Health, The Royal Free Hospital, Pond Street, London NW3 2PF, United Kingdom.
authors.forename: Nathan
authors.initials: N
authors.lastname: Davies
authors.affiliation: Liver Failure Group, UCL Institute for Liver and Digestive Health, The Royal Free Hospital, Pond Street, London NW3 2PF, United Kingdom. Electronic address: r.jalan@ucl.ac.uk.
authors.forename: Rajiv
authors.initials: R
authors.lastname: Jalan
mesh_terms: D000418:Albumins / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000378:metabolism; D004195:Disease Models, Animal; D058625:End Stage Liver Disease / Q000378:metabolism* / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000378:metabolism / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D000418:Albumins; D017382:Reactive Oxygen Species; D014841:von Willebrand Factor; C018524:N,N-dimethylarginine; D001120:Arginine; D019001:Nitric Oxide Synthase
keywords: Albumin; Endothelial dysfunction; Human umbilical vein endothelial cells; Liver cirrhosis; Rat