The Endothelial Glycocalyx as a Target of Excess Soluble Fms-like Tyrosine Kinase-1

Schulz, Annika; Drost, Carolin C.; Hesse, Bettina; Beul, Katrin; Boeckel, Göran R.; Lukasz, Alexander; Pavenstädt, Hermann; Brand, Marcus; Di Marco, Giovana S.

doi:10.3390/ijms24065380

Open AccessArticle

The Endothelial Glycocalyx as a Target of Excess Soluble Fms-like Tyrosine Kinase-1

by

Annika Schulz

,

Carolin C. Drost

,

Bettina Hesse

,

Katrin Beul

,

Göran R. Boeckel

,

Alexander Lukasz

,

Hermann Pavenstädt

,

Marcus Brand

and

Giovana S. Di Marco

^*

Department of Internal Medicine D, University Hospital Münster, 48149 Münster, Germany

^*

Author to whom correspondence should be addressed.

Int. J. Mol. Sci. 2023, 24(6), 5380; https://doi.org/10.3390/ijms24065380

Submission received: 13 February 2023 / Revised: 8 March 2023 / Accepted: 9 March 2023 / Published: 11 March 2023

(This article belongs to the Special Issue New Insights into Endothelial Injury)

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Abstract

Soluble fms-like tyrosine kinase-1 (sFlt-1) is a secreted protein that binds heparan sulfate expressed on the endothelial glycocalyx (eGC). In this paper we analyze how excess sFlt-1 causes conformational changes in the eGC, leading to monocyte adhesion, a key event triggering vascular dysfunction. In vitro exposure of primary human umbilical vein endothelial cells to excess sFlt-1 decreased eGC height and increased stiffness as determined by atomic force microscopy (AFM). Yet, structural loss of the eGC components was not observed, as indicated by Ulex europaeus agglutinin I and wheat germ agglutinin staining. Moreover, the conformation observed under excess sFlt-1, a collapsed eGC, is flat and stiff with unchanged coverage and sustained content. Functionally, this conformation increased the endothelial adhesiveness to THP-1 monocytes by about 35%. Heparin blocked all these effects, but the vascular endothelial growth factor did not. In vivo administration of sFlt-1 in mice also resulted in the collapse of the eGC in isolated aorta analyzed ex vivo by AFM. Our findings show that excess sFlt-1 causes the collapse of the eGC and favors leukocyte adhesion. This study provides an additional mechanism of action by which sFlt-1 may cause endothelial dysfunction and injury.

Keywords: endothelial glycocalyx; soluble fms-like tyrosine kinase-1 (sFlt-1); heparin; endothelial dysfunction; endothelial injury; monocyte adhesion

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MDPI and ACS Style

Schulz, A.; Drost, C.C.; Hesse, B.; Beul, K.; Boeckel, G.R.; Lukasz, A.; Pavenstädt, H.; Brand, M.; Di Marco, G.S. The Endothelial Glycocalyx as a Target of Excess Soluble Fms-like Tyrosine Kinase-1. Int. J. Mol. Sci. 2023, 24, 5380. https://doi.org/10.3390/ijms24065380

AMA Style

Schulz A, Drost CC, Hesse B, Beul K, Boeckel GR, Lukasz A, Pavenstädt H, Brand M, Di Marco GS. The Endothelial Glycocalyx as a Target of Excess Soluble Fms-like Tyrosine Kinase-1. International Journal of Molecular Sciences. 2023; 24(6):5380. https://doi.org/10.3390/ijms24065380

Chicago/Turabian Style

Schulz, Annika, Carolin C. Drost, Bettina Hesse, Katrin Beul, Göran R. Boeckel, Alexander Lukasz, Hermann Pavenstädt, Marcus Brand, and Giovana S. Di Marco. 2023. "The Endothelial Glycocalyx as a Target of Excess Soluble Fms-like Tyrosine Kinase-1" International Journal of Molecular Sciences 24, no. 6: 5380. https://doi.org/10.3390/ijms24065380

APA Style

Schulz, A., Drost, C. C., Hesse, B., Beul, K., Boeckel, G. R., Lukasz, A., Pavenstädt, H., Brand, M., & Di Marco, G. S. (2023). The Endothelial Glycocalyx as a Target of Excess Soluble Fms-like Tyrosine Kinase-1. International Journal of Molecular Sciences, 24(6), 5380. https://doi.org/10.3390/ijms24065380

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The Endothelial Glycocalyx as a Target of Excess Soluble Fms-like Tyrosine Kinase-1

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