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Title: | Sinusoidal Endothelial Dysfunction Precedes Inflammation and Fibrosis in a Model of NAFLD |
Author: | Pasarín Castellanos, Marcos La Mura, Vincenzo Gracia-Sancho, Jorge García Calderó, Héctor Rodríguez Vilarrupla, Aina García Pagán, Juan Carlos Bosch i Genover, Jaume González-Abraldes Iglesias, Juan |
Keywords: | Malalties del fetge Endoteli Fibrosi pulmonar Liver diseases Endothelium Pulmonary fibrosis |
Issue Date: | 3-Apr-2012 |
Publisher: | Public Library of Science (PLoS) |
Abstract: | Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome. Most morbidity associated with the metabolic syndrome is related to vascular complications, in which endothelial dysfunction is a major pathogenic factor. However, whether NAFLD is associated with endothelial dysfunction within the hepatic vasculature is unknown. The aims of this study were to explore, in a model of diet-induced overweight that expresses most features of the metabolic syndrome, whether early NAFLD is associated with liver endothelial dysfunction. Wistar Kyoto rats were fed a cafeteria diet (CafD; 65% of fat, mostly saturated) or a control diet (CD) for 1 month. CafD rats developed features of the metabolic syndrome (overweight, arterial hypertension, hypertryglyceridemia, hyperglucemia and insulin resistance) and liver steatosis without inflammation or fibrosis. CafD rats had a significantly higher in vivo hepatic vascular resistance than CD. In liver perfusion livers from CafD rats had an increased portal perfusion pressure and decreased endothelium-dependent vasodilation. This was associated with a decreased Akt-dependent eNOS phosphorylation and NOS activity. In summary, we demonstrate in a rat model of the metabolic syndrome that shows features of NAFLD, that liver endothelial dysfunction occurs before the development of fibrosis or inflammation. |
Note: | Reproducció del document publicat a: http://dx.doi.org/10.1371/journal.pone.0032785 |
It is part of: | PLoS One, 2012, vol. 7, num. 2, p. e32785 |
URI: | http://hdl.handle.net/2445/43658 |
Related resource: | http://dx.doi.org/10.1371/journal.pone.0032785 |
ISSN: | 1932-6203 |
Appears in Collections: | Articles publicats en revistes (Medicina) |
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