Immunomodulatory and antioxidant function of albumin stabilises the endothelium and improves survival in a rodent model of chronic liver failure

• DOI: 10.1016/j.jhep.2014.10.031
• Publication Date: 2014-10-30T19:02:41Z
• Authors: Rita Garcia-Martinez; Fausto Andreola; Gautam Mehta; Katie Poulton; Marc Oria; Maria Jover; Junpei Soeda; Jane Macnaughtan; Francesco De Chiara; Abeba Habtesion; Rajeshwar P. Mook...; Nathan Davies; Rajiv Jalan
• Keywords: Inflammation; 0303 health sciences; Hemodynamics; Arginine; Rats; 3. Good health; End Stage Liver Disease; Rats, Sprague-Dawley; Disease Models, Animal; Oxidative Stress; 03 medical and health sciences; Albumins; von Willebrand Factor; Animals; Humans; Endothelium, Vascular; Nitric Oxide Synthase; Reactive Oxygen Species

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.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.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.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.