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|Title:||Sinusoidal Endothelial Dysfunction Precedes Inflammation and Fibrosis in a Model of NAFLD|
La Mura, V.
García Calderó, H.
Rodríguez Vilarrupla, A.
García Pagán, Juan Carlos
Bosch i Genover, Jaume
González-Abraldes Iglesias, Juan
|Keywords:||Malalties del fetge|
|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|
|Appears in Collections:||Articles publicats en revistes (Medicina)|
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