The endothelial function biomarker soluble E‐selectin is associated with nonalcoholic fatty liver disease
Liver International, vol. 40, pp. 1079–1088
Abstract
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 13
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Maastricht University Medical Centre · Maastricht University
Affiliation as printed
CARIM School for Cardiovascular Diseases Maastricht University Maastricht The Netherlands
Department of Internal Medicine Division of Endocrinology and Metabolic Diseases Maastricht University Medical Center Maastricht The Netherlands
Department of Internal Medicine Division of General Internal Medicine Laboratory for Metabolism and Vascular Medicine Maastricht University Medical Center Maastricht The Netherlands
CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, The Netherlands
Department of Internal Medicine, Division of Endocrinology and Metabolic Diseases, Maastricht University Medical Center, Maastricht, The Netherlands
Department of Internal Medicine, Division of General Internal Medicine, Laboratory for Metabolism and Vascular Medicine, Maastricht University Medical Center, Maastricht, The Netherlands
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Maastricht University Medical Centre · Maastricht University
Affiliation as printed
CARIM School for Cardiovascular Diseases Maastricht University Maastricht The Netherlands
Department of Internal Medicine Division of General Internal Medicine Laboratory for Metabolism and Vascular Medicine Maastricht University Medical Center Maastricht The Netherlands
CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, The Netherlands
Department of Internal Medicine, Division of General Internal Medicine, Laboratory for Metabolism and Vascular Medicine, Maastricht University Medical Center, Maastricht, The Netherlands
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Maastricht University Medical Centre · Maastricht University
Affiliation as printed
CARIM School for Cardiovascular Diseases Maastricht University Maastricht The Netherlands
Department of Internal Medicine Division of General Internal Medicine Laboratory for Metabolism and Vascular Medicine Maastricht University Medical Center Maastricht The Netherlands
CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, The Netherlands
Department of Internal Medicine, Division of General Internal Medicine, Laboratory for Metabolism and Vascular Medicine, Maastricht University Medical Center, Maastricht, The Netherlands
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Maastricht University Medical Centre · Maastricht University
Affiliation as printed
Department of General Surgery Maastricht University Medical Center Maastricht The Netherlands
NUTRIM School of Nutrition and Translational Research in Metabolism Maastricht University Maastricht The Netherlands
Department of General Surgery, Maastricht University Medical Center, Maastricht, The Netherlands
NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands
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University Medical Center Utrecht · Amsterdam Public Health · Amsterdam University Medical Centers · Amsterdam UMC Location Vrije Universiteit Amsterdam
Affiliation as printed
Department of Epidemiology and Biostatistics Amsterdam University Medical Center – location VUmc the Amsterdam Public Health Research Institute Amsterdam Amsterdam The Netherlands
Julius Center for Health Sciences and Primary Care University Medical Center Utrecht Utrecht The Netherlands
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Maastricht University Medical Centre · Maastricht University
Affiliation as printed
CARIM School for Cardiovascular Diseases Maastricht University Maastricht The Netherlands
Department of Internal Medicine Division of General Internal Medicine Laboratory for Metabolism and Vascular Medicine Maastricht University Medical Center Maastricht The Netherlands
CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, The Netherlands
Department of Internal Medicine, Division of General Internal Medicine, Laboratory for Metabolism and Vascular Medicine, Maastricht University Medical Center, Maastricht, The Netherlands
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Leen M. ‘t Hart Aachen Department of Biomedical Data Sciences Section Molecular Epidemiology Leiden University Medical Center Leiden The Netherlands Department of Cell and Chemical Biology Leiden University Medical Center Leiden the Netherlands Department of Cell and Chemical Biology
Leiden University Medical Center · Amsterdam Public Health · Amsterdam University Medical Centers · Amsterdam UMC Location Vrije Universiteit Amsterdam
Affiliation as printed
Department of Biomedical Data Sciences Section Molecular Epidemiology Leiden University Medical Center Leiden The Netherlands
Department of Cell and Chemical Biology Leiden University Medical Center Leiden The Netherlands
Department of Epidemiology and Biostatistics Amsterdam University Medical Center – location VUmc the Amsterdam Public Health Research Institute Amsterdam Amsterdam The Netherlands
Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, The Netherlands
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Maastricht University Medical Centre · Maastricht University · Zuyderland Medisch Centrum
Affiliation as printed
Department of General Surgery Maastricht University Medical Center Maastricht The Netherlands
Department of General Surgery Zuyderland Medical Center Heerlen The Netherlands
NUTRIM School of Nutrition and Translational Research in Metabolism Maastricht University Maastricht The Netherlands
Department of General Surgery, Maastricht University Medical Center, Maastricht, The Netherlands
Department of General Surgery, Zuyderland Medical Center, Heerlen, The Netherlands
NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands
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Maastricht University Medical Centre · Maastricht University
Affiliation as printed
CARIM School for Cardiovascular Diseases Maastricht University Maastricht The Netherlands
Department of Internal Medicine Division of General Internal Medicine Laboratory for Metabolism and Vascular Medicine Maastricht University Medical Center Maastricht The Netherlands
CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, The Netherlands
Department of Internal Medicine, Division of General Internal Medicine, Laboratory for Metabolism and Vascular Medicine, Maastricht University Medical Center, Maastricht, The Netherlands
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Maastricht University Medical Centre · Maastricht University · Care and Public Health Research Institute
Affiliation as printed
CAPHRI School for Public Health and Primary Care Maastricht University Maastricht The Netherlands
CARIM School for Cardiovascular Diseases Maastricht University Maastricht The Netherlands
Department of Internal Medicine Division of Endocrinology and Metabolic Diseases Maastricht University Medical Center Maastricht The Netherlands
CAPHRI School for Public Health and Primary Care, Maastricht University, Maastricht, The Netherlands
CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, The Netherlands
Department of Internal Medicine, Division of Endocrinology and Metabolic Diseases, Maastricht University Medical Center, Maastricht, The Netherlands
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Maastricht University Medical Centre · Maastricht University
Affiliation as printed
CARIM School for Cardiovascular Diseases Maastricht University Maastricht The Netherlands
Department of Internal Medicine Division of General Internal Medicine Laboratory for Metabolism and Vascular Medicine Maastricht University Medical Center Maastricht The Netherlands
CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, The Netherlands
Department of Internal Medicine, Division of General Internal Medicine, Laboratory for Metabolism and Vascular Medicine, Maastricht University Medical Center, Maastricht, The Netherlands
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Maastricht University Medical Centre · Maastricht University
Affiliation as printed
CARIM School for Cardiovascular Diseases Maastricht University Maastricht The Netherlands
Department of Internal Medicine Division of General Internal Medicine Laboratory for Metabolism and Vascular Medicine Maastricht University Medical Center Maastricht The Netherlands
Department of Internal Medicine Division of General Internal Medicine Maastricht University Medical Center Maastricht The Netherlands
CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, The Netherlands
Department of Internal Medicine, Division of General Internal Medicine, Laboratory for Metabolism and Vascular Medicine, Maastricht University Medical Center, Maastricht, The Netherlands
Department of Internal Medicine, Division of General Internal Medicine, Maastricht University Medical Center, Maastricht, The Netherlands
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Martijn C.G.J. Brouwers corresponding
Maastricht University Medical Centre · Maastricht University
Affiliation as printed
CARIM School for Cardiovascular Diseases Maastricht University Maastricht The Netherlands
Department of Internal Medicine Division of Endocrinology and Metabolic Diseases Maastricht University Medical Center Maastricht The Netherlands
Department of Internal Medicine Division of General Internal Medicine Laboratory for Metabolism and Vascular Medicine Maastricht University Medical Center Maastricht The Netherlands
CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, The Netherlands
Department of Internal Medicine, Division of Endocrinology and Metabolic Diseases, Maastricht University Medical Center, Maastricht, The Netherlands
Department of Internal Medicine, Division of General Internal Medicine, Laboratory for Metabolism and Vascular Medicine, Maastricht University Medical Center, Maastricht, The Netherlands
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