title: Nanomechanics of the endothelial glycocalyx contribute to Na+-induced vascular inflammation.
abstract: High dietary salt (NaCl) is a known risk factor for cardiovascular pathologies and inflammation. High plasma Na+concentrations (high Na+) have been shown to stiffen the endothelial cortex and decrease nitric oxide (NO) release, a hallmark of endothelial dysfunction. Here we report that chronic high Na+damages the endothelial glycocalyx (eGC), induces release of inflammatory cytokines from the endothelium and promotes monocyte adhesion. Single cell force spectroscopy reveals that high Na+enhances vascular adhesion protein-1 (VCAM-1)-dependent adhesion forces between monocytes and endothelial surface, giving rise to increased numbers of adherent monocytes on the endothelial surface. Mineralocorticoid receptor antagonism with spironolactone prevents high Na+-induced eGC deterioration, decreases monocyte-endothelium interactions, and restores endothelial function, indicated by increased release of NO. Whereas high Na+decreases NO release, it induces endothelial release of the pro-inflammatory cytokines IL-1ß and TNFα. However, in contrast to chronic salt load (hours), in vivo and in vitro, an acute salt challenge (minutes) does not impair eGC function. This study identifies the eGC as important mediator of inflammatory processes and might further explain how dietary salt contributes to endothelialitis and cardiovascular pathologies by linking endothelial nanomechanics with vascular inflammation.
authors.affiliation: Institute of Physiology II, University of Münster, 48149 Münster, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Schierke
authors.affiliation: Institute of Physiology II, University of Münster, 48149 Münster, Germany.
authors.forename: Margot J
authors.initials: MJ
authors.lastname: Wyrwoll
authors.affiliation: Institute of Physiology II, University of Münster, 48149 Münster, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Wisdorf
authors.affiliation: Institute of Physiology II, University of Münster, 48149 Münster, Germany.
authors.forename: Leon
authors.initials: L
authors.lastname: Niedzielski
authors.affiliation: Institute of Physiology II, University of Münster, 48149 Münster, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Maase
authors.affiliation: Department of Neurology, University of Münster, 48149 Münster, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Ruck
authors.affiliation: Department of Neurology, University of Münster, 48149 Münster, Germany.
authors.forename: Sven G
authors.initials: SG
authors.lastname: Meuth
authors.affiliation: Institute of Physiology II, University of Münster, 48149 Münster, Germany.
authors.forename: Kristina
authors.initials: K
authors.lastname: Kusche-Vihrog
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D002448:Cell Adhesion; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000276:immunology / Q000378:metabolism*; D019276:Glycocalyx / Q000378:metabolism*; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D051379:Mice; D009000:Monocytes / Q000166:cytology / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D017673:Sodium Chloride, Dietary / Q000009:adverse effects*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014657:Vasculitis / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism*
chemical_list: D053583:Interleukin-1beta; D017673:Sodium Chloride, Dietary; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide