Thromb Haemost 2011; 105(05): 790-801
DOI: 10.1160/TH10-08-0560
Theme Issue Article
Schattauer GmbH

Degradation of the endothelial glycocalyx is associated with chylomicron leakage in mouse cremaster muscle microcirculation

Alina A. Constantinescu
1   Department of Medical Physics, Academic Medical Center, Amsterdam, the Netherlands
,
Jos A. E. Spaan
1   Department of Medical Physics, Academic Medical Center, Amsterdam, the Netherlands
,
E. Karin Arkenbout
2   Department of Medical Biochemistry, Academic Medical Center, Amsterdam, the Netherlands
,
Hans Vink
3   Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands
4   Department of Physiology, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands
,
Jurgen W. G. E. VanTeeffelen
4   Department of Physiology, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands
› Institutsangaben
Financial support: This work was supported by the Netherlands Organization for Scientific Research (NWO, grant no. 902–16–192) and the Netherlands Heart Foundation (grant no. 2005T037).
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Publikationsverlauf

Received: 31. August 2010

Accepted after minor revision: 09. November 2010

Publikationsdatum:
28. November 2017 (online)

Summary

A thick endothelial glycocalyx contributes to the barrier function of vascular endothelium in macro- and microcirculation. We hypothesised in the current study that diet-induced hyperlipidaemia perturbs the glycocalyx, resulting in decreased dimensions of this layer and increased transendothelial lipoprotein leakage in capillaries. Glycocalyx thickness was measured in mouse cremaster muscle capillaries by intravital microscopy from the distance between flowing red blood cells and the endothelial surface. In control C57BL/6 mice on standard chow, glycocalyx thickness measured 0.58 ± 0.01 (mean ± SEM) μm, and no lipo-proteins were observed in the tissue. After three months administration of an either mild or severe high-fat / high-cholesterol diet (HFC) to C57BL/6 and ApoE3-Leiden mice, circulating large lipoproteins appeared into the subendothelial space in an increasing proportion of cre-master capillaries, and these capillaries displayed reduced glycocalyx dimensions of 0.40 ± 0.02 and 0.30 ± 0.01 μm (C57BL/6 mice), and 0.37 ± 0.01 and 0.28 ± 0.01 μm (ApoE3-Leiden mice), after the mild and severe HFC diet, respectively. The chylomicron nature of the accumulated lipoproteins was confirmed by observations of subendothelial deposition of DiI-labeled chylomicrons in capillaries after inducing acute glycocalyx degradation by heparitinase in normolipidaemic C57BL/6 mice. It is concluded that while under control conditions the endothelial glycocalyx contributes to the vascular barrier against transvascular lipoprotein leakage in the microcirculation, diet-induced hyperlipidaemia reduces the thickness of the glycocalyx, thereby facilitating leakage of chylomicrons across the capillary wall.

 
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