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The endothelial function biomarker soluble E-selectin is associated with nonalcoholic fatty liver disease.


ABSTRACT: BACKGROUND & AIMS:Plasma soluble E-selectin (sE-selectin) is a frequently used biomarker of systemic endothelial dysfunction. The present study explored the relationship between nonalcoholic fatty liver disease (NAFLD) and plasma sE-selectin levels. METHODS:Expression of E-selectin in liver, visceral adipose tissue (VAT) and muscle was studied in relation to plasma sE-selectin in severely obese individuals (n = 74). The course of hepatic E-selectin expression in relation to hepatic steatosis and inflammation was examined in C57BL/6J LDLR-/- mice on a Western-type diet. The relationship between biomarkers of NAFLD, that is, plasma aminotransferase (ALT) and NAFLD susceptibility genes (rs738409 [PNPLA3] and rs1260326 [GCKR]), and plasma sE-selectin was studied in the combined CODAM (n = 571) and Hoorn (n = 694) studies. RESULTS:E-selectin expression in liver, not VAT or muscle, was associated with plasma sE-selectin in severely obese individuals (? = 0.26; 95% CI: 0.05-0.47). NAFLD severity was associated with hepatic E-selectin expression (P = .02) and plasma sE-selectin (P = .003). LDLR-/- mice on a Western-type diet displayed increased hepatic E-selectin expression that followed the same course as hepatic inflammation, but not steatosis. In the CODAM study, plasma ALT was associated with plasma sE-selectin, independent of potential confounders (? = 0.25; 95% CI: 0.16-0.34). Both rs738409 and rs1260326 were associated with higher plasma sE-selectin in the combined CODAM and Hoorn studies (P = .01 and P = .004 respectively). CONCLUSIONS:NAFLD and related markers are associated with higher expression of hepatic E-selectin and higher levels of plasma sE-selectin. Further studies are required to investigate the role of E-selectin in the pathogenesis of NAFLD and the applicability of sE-selectin as a plasma biomarker of NAFLD/NASH.

SUBMITTER: Simons N 

PROVIDER: S-EPMC7317803 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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The endothelial function biomarker soluble E-selectin is associated with nonalcoholic fatty liver disease.

Simons Nynke N   Bijnen Mitchell M   Wouters Kristiaan A M KAM   Rensen Sander S SS   Beulens Joline W J JWJ   van Greevenbroek Marleen M J MMJ   't Hart Leen M LM   Greve Jan Willem M JWM   van der Kallen Carla J H CJH   Schaper Nicolaas C NC   Schalkwijk Casper G CG   Stehouwer Coen D A CDA   Brouwers Martijn C G J MCGJ  

Liver international : official journal of the International Association for the Study of the Liver 20200129 5


<h4>Background & aims</h4>Plasma soluble E-selectin (sE-selectin) is a frequently used biomarker of systemic endothelial dysfunction. The present study explored the relationship between nonalcoholic fatty liver disease (NAFLD) and plasma sE-selectin levels.<h4>Methods</h4>Expression of E-selectin in liver, visceral adipose tissue (VAT) and muscle was studied in relation to plasma sE-selectin in severely obese individuals (n = 74). The course of hepatic E-selectin expression in relation to hepati  ...[more]

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