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Sinusoidal Endothelial Dysfunction Precedes Inflammation and Fibrosis in a Model of NAFLD
Pasarín, M.; La Mura, V.; Gracia-Sancho, Jorge; García Calderó, H.; Rodríguez Vilarrupla, A.; García Pagán, Juan Carlos; Bosch i Genover, Jaume; González-Abraldes Iglesias, Juan
Universitat de Barcelona
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.
Malalties del fetge
Endoteli
Fibrosi pulmonar
Liver diseases
Endothelium
Pulmonary fibrosis
cc-by (c) Pasarín, M. et al., 2012
http://creativecommons.org/licenses/by/3.0/es
Article
info:eu-repo/semantics/publishedVersion
Public Library of Science (PLoS)
         

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