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.
| Original language | English |
|---|---|
| Article number | 46476 |
| Journal | Scientific Reports |
| Volume | 7 |
| ISSN | 2045-2322 |
| DOIs | |
| Publication status | Published - 13.04.2017 |
Funding
We thank Prof. Hans Oberleithner (Institute of Physiology II, University of M?nster) for support and discussion in this study, Marianne Wilhelmi and Sergej Handel (Institute of Physiology II, University of M?nster) for the excellent technical assistance. The authors thank Dr. Peter Hanley (Institute of Molecular Cell Biology, University of M?nster) for fruitful discussions and critically reading the manuscript. We are grateful to the group of Prof. H. Omran (Pediatric department, University of M?nster) for help with the quantification of the NO concentration. This work was supported by grants from the Deutsche Forschungsgemeinschaft (KU 1496/7-1, KU 1496/7-3 and Koselleck grant OB 63/18), and by the Centre of Excellence (Cells in Motion; CIM), University of M?nster. We are grateful to COST Action TD1002 as well as COST Action BM1301 for supporting networking activities.
