Symmetric dimethylarginine in dysfunctional high-density lipoprotein mediates endothelial glycocalyx breakdown in chronic kidney disease

Bettina Hesse, Alexandros Rovas, Konrad Buscher, Kristina Kusche-Vihrog, Marcus Brand, Giovana Seno Di Marco, Jan T. Kielstein, Hermann Pavenstädt, Wolfgang A. Linke, Jerzy Roch Nofer, Philipp Kümpers, Alexander Lukasz*

*Corresponding author for this work
2 Citations (Scopus)


Dysfunctional high-density lipoprotein (d-HDL) in chronic kidney disease is known to have a change in composition towards an endothelial-damaging phenotype, amongst others, via the accumulation of symmetric dimethylarginine. The endothelial glycocalyx, a carbohydrate-rich layer lining the endothelial luminal surface, is a first line defense against vascular diseases including atherosclerosis. Here we conducted a translational, cross-sectional study to determine the role of symmetric dimethylarginine in d-HDL as a mediator of glycocalyx damage. Using confocal and atomic force microscopy, intact HDL from healthy donors was found to maintain the glycocalyx while isolated HDL from hemodialysis patients and exogenous symmetric dimethylarginine caused significant damage to the glycocalyx in endothelial cells in vitro in a dose-dependent manner. Symmetric dimethylarginine triggered glycocalyx deterioration via molecular pathways mediated by toll-like-receptor 2 and matrix metalloprotease-9. Corresponding intravital microscopy revealed that exogenous symmetric dimethylarginine and d-HDL from hemodialysis patients caused glycocalyx breakdown, which subsequently contributed to alterations in leukocyte rolling. Biologically effective HDL, which estimates the functionality of HDL, was calculated from circulating HDL-cholesterol and symmetric dimethylarginine, as described in the literature. Biologically effective HDL was the only parameter that could independently predict glycocalyx damage in vivo. Thus, our data suggest that symmetric dimethylarginine in d-HDL mediates glycocalyx breakdown in chronic kidney disease.

Original languageEnglish
JournalKidney International
Issue number3
Pages (from-to)502-515
Number of pages14
Publication statusPublished - 01.03.2020

Research Areas and Centers

  • Academic Focus: Center for Brain, Behavior and Metabolism (CBBM)


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