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

Abstract

Backgroud & 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, i.e. 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=0.02) and plasma sE‐selectin (p=0.003). 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=0.01 and p=0.004, 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.