Rita Garcia-Martinez1, Fausto Andreola1, Gautam Mehta1, Katie Poulton2, Marc Oria1, Maria Jover1, Junpei Soeda3, Jane Macnaughtan1, Francesco De Chiara1, Abeba Habtesion1, Rajeshwar P Mookerjee1, Nathan Davies1, Rajiv Jalan4. 1. Liver Failure Group, UCL Institute for Liver and Digestive Health, The Royal Free Hospital, Pond Street, London NW3 2PF, United Kingdom. 2. Division of Medicine, University College London, London, United Kingdom. 3. Center for Hepatology, UCL Institute for Liver and Digestive Health, The Royal Free Hospital, Pond Street, London NW3 2PF, United Kingdom. 4. 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.
Abstract
BACKGROUND & AIMS: 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.
BACKGROUND & AIMS: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: Andrea Morotti; Sandro Marini; Umme K Lena; Katherine Crawford; Kristin Schwab; Christina Kourkoulis; Alison M Ayres; M Edip Gurol; Anand Viswanathan; Steven M Greenberg; Christopher D Anderson; Jonathan Rosand; Joshua N Goldstein Journal: J Neurol Date: 2017-03-10 Impact factor: 4.849
Authors: Nga Phi Thi Nguyen; Thuc Luong Cong; Binh Thanh Vu; Tuan Dinh Le; Thi Thanh Hoa Tran; Binh Nhu Do; Son Tien Nguyen; Lan Ho Thi Nguyen; Manh Van Ngo; Hoa Trung Dinh; Hoang Duong Huy; Nghia Xuan Vu; Kien Nguyen Trung; Duong Ngoc Vu; Nghia The Pham Journal: Int J Gen Med Date: 2022-03-08