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 (β = 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 (β = 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.

• Authors: Nynke Simons, Mitchell Bijnen, Kristiaan A M Wouters, Sander S Rensen, Joline W J Beulens, Marleen M J van Greevenbroek, Leen M 't Hart, Jan Willem M Greve, Carla J H van der Kallen, Nicolaas C Schaper, Casper G Schalkwijk, Coen D A Stehouwer, Martijn C G J Brouwers
• Journal: Liver international : official journal of the International Association for the Study of the Liver (Liver Int) Vol. 40 Issue 5 Pg. 1079-1088 (05 2020) ISSN: 1478-3231 [Electronic] United States
• PMID: 31960587 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 The Authors. Liver International published by John Wiley & Sons Ltd.

Chemical References

• Adaptor Proteins, Signal Transducing
• Biomarkers
• Cadherins
• Cdh1 protein, mouse
• Gckr protein, mouse
• Lipase
• PNPLA3 protein, mouse
• Phospholipases A2, Calcium-Independent

Topics

• Adaptor Proteins, Signal Transducing
• Animals
• Biomarkers
• Cadherins (genetics)
• Lipase
• Liver
• Mice
• Mice, Inbred C57BL
• Non-alcoholic Fatty Liver Disease (genetics)
• Phospholipases A2, Calcium-Independent