Format

Send to

Choose Destination
Atherosclerosis. 2009 Jan;202(1):296-303. doi: 10.1016/j.atherosclerosis.2008.03.024. Epub 2008 Apr 12.

Tumor necrosis factor-alpha inhibition protects against endotoxin-induced endothelial glycocalyx perturbation.

Author information

1
Department of Vascular Medicine, Academic Medical Centre, University of Amsterdam, The Netherlands.

Abstract

OBJECTIVE:

Inflammatory stimuli profoundly increase the vulnerability of the vessel wall to atherogenesis. The endothelial glycocalyx, a layer of glycosaminoglycans and proteoglycans covering the luminal side of the vasculature, has recently emerged as an orchestrator of vascular homeostasis. In the present study, we investigated whether endotoxin-induced inflammatory reactions lead to a decrease of endothelial glycocalyx thickness in humans and whether tumor necrosis factor-alpha (TNFalpha) plays a role in this process.

DESIGN, SUBJECTS AND INTERVENTION:

Healthy male volunteers received low-dose endotoxin (1ng/kg) intravenously, with (n=8) or without (n=13) pre-treatment with the soluble TNFalpha receptor etanercept. Endothelial glycocalyx thickness and related parameters were determined after endotoxin challenge.

RESULTS:

Endotoxin resulted in a profound reduction in microvascular glycocalyx thickness (from 0.60+/-0.1 to 0.30+/-0.1microm, p<0.01). Concomitantly, plasma levels of the principal glycocalyx constituent hyaluronan (62+/-18 to 85+/-24ng/mL, p<0.05), monocyte activation and coagulation activation increased (F1+2; 0.3+/-0.1 to 2.8+/-1.5nmol/L, p<0.05 and d-dimer; from 0.2+/-0.1 to 0.4+/-0.1mg/L, p<0.05 compared to baseline). Inhibition of TNFalpha by etanercept attenuated loss of microvascular glycocalyx thickness (0.54+/-0.1 to 0.35+/-0.1mum, p<0.05). Changes in hyaluronan (58+/-13 to 46+/-10ng/mL, p<0.05) and coagulation activation were also attenuated (F1+2; 0.3+/-0.1 to 2.1+/-0.9nmol/L and d-dimer; from 0.2+/-0.1 to 0.3+/-0.1mg/L, p<0.05 compared to baseline).

CONCLUSIONS:

These data suggest that inflammatory activity, in part mediated by TNFalpha, leads to perturbation of the endothelial glycocalyx in humans. This may contribute to the vascular vulnerability induced by inflammation.

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center