title: Inflammation-induced increases in plasma endocan levels are associated with endothelial dysfunction in humans in vivo.
abstract: Although endothelial dysfunction is central to the pathogenesis of sepsis, no specific and clinically applicable marker for endothelial dysfunction is currently available. Endocan, a proteoglycan excreted by endothelial cells in response to inflammatory cytokines, may serve as such a marker. Our objective was to investigate the kinetics of endocan and its relationship with inflammation-induced endothelial dysfunction during experimental human endotoxemia. Endothelial function was assessed in 17 healthy male volunteers before and 4 h after the administration of 2 ng/kg lipopolysaccharide (LPS) by determination of the vasodilatory response of forearm blood vessels to intra-arterial infusion of endothelium-dependent (acetylcholine) or endothelium-independent (nitroglycerin/sodium nitroprusside) vasodilators using venous occlusion plethysmography. Plasma levels of endocan, inflammatory cytokines, intercellular adhesion molecule (ICAM), and vascular cell adhesion molecule (VCAM) were measured, and correlations with endothelial dysfunction were explored. Plasma levels of all measured cytokines, endocan, ICAM, and VCAM concentrations significantly increased after LPS administration. Furthermore, LPS administration resulted in a significantly blunted response to acetylcholine (mean ± SD increase in forearm blood flow [FBF] of 383% ± 320% before LPS vs. 173% ± 134% after LPS, P = 0.03), whereas the response to nitroglycerin/sodium nitroprusside was not affected (mean ± SD increase in FBF of 174% ± 120% before LPS vs. 110% ± 82% after LPS, P = 0.11). Furthermore, there was a significant correlation between the increase in plasma endocan levels and the attenuation of vasodilatory responses to acetylcholine (r = -0.48, P < 0.05). No correlation existed between plasma levels of ICAM or VCAM and the attenuation of the acetylcholine-induced vasodilatory response. Endocan levels are related to endothelial dysfunction in humans in vivo during systemic inflammation evoked by experimental endotoxemia. Therefore, this study suggests that endocan could be a novel marker of endothelial dysfunction in inflammatory conditions.
authors.affiliation: *Departments of Anesthesiology, Pain and Palliative Medicine, and †Intensive Care Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Laura A E
authors.initials: LA
authors.lastname: Cox
authors.forename: Lucas T
authors.initials: LT
authors.lastname: van Eijk
authors.forename: Bart P C
authors.initials: BP
authors.lastname: Ramakers
authors.forename: Mirrin J
authors.initials: MJ
authors.lastname: Dorresteijn
authors.forename: Jelle
authors.initials: J
authors.lastname: Gerretsen
authors.forename: Matthijs
authors.initials: M
authors.lastname: Kox
authors.forename: Peter
authors.initials: P
authors.lastname: Pickkers
mesh_terms: D000328:Adult; D001783:Blood Flow Velocity; D004730:Endothelium, Vascular / Q000473:pathology*; D019446:Endotoxemia / Q000097:blood / Q000473:pathology / Q000503:physiopathology; D005542:Forearm / Q000473:pathology; D064368:Healthy Volunteers; D006801:Humans; D007249:Inflammation / Q000503:physiopathology*; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D008070:Lipopolysaccharides / Q000737:chemistry; D008297:Male; D009363:Neoplasm Proteins / Q000097:blood*; D005996:Nitroglycerin / Q000737:chemistry; D009599:Nitroprusside / Q000737:chemistry; D011509:Proteoglycans / Q000097:blood*; D012107:Research Design; D018805:Sepsis / Q000503:physiopathology*; D013997:Time Factors; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology; D055815:Young Adult
chemical_list: C101134:ESM1 protein, human; D008070:Lipopolysaccharides; D009363:Neoplasm Proteins; D011509:Proteoglycans; D019010:Vascular Cell Adhesion Molecule-1; D014665:Vasodilator Agents; D018799:Intercellular Adhesion Molecule-1; D009599:Nitroprusside; D005996:Nitroglycerin