# Glycocalyx strengthens endothelial barrier function and protects from angioedema inducing compounds

## TL;DR

The endothelial glycocalyx helps protect against angioedema by maintaining vascular barrier integrity, and its degradation increases permeability.

## Contribution

This study demonstrates the protective role of the glycocalyx in angioedema and suggests its potential as a biomarker.

## Key findings

- Glycocalyx degradation increases endothelial permeability and may contribute to edema development.
- Histamine reduces glycocalyx integrity, while bradykinin and serotonin do not.
- Glycocalyx degradation enhances mediator-induced water permeability without additive effects on TEER.

## Abstract

Hereditary angioedema (HAE) and mast cell-mediated angioedema are characterized by episodic swelling. Yet, atypical variants, such as HAE with normal C1 inhibitor, remain poorly understood and diagnostically challenging. Although advances in diagnosis and therapy have improved patient outcomes, investigating the role of the endothelial glycocalyx in regulating vascular permeability may uncover novel biomarkers and enhance both diagnostic and prognostic strategies.

Human umbilical vein endothelial cells (HUVEC) were treated with enzymes for glycocalyx degradation. Glycocalyx quantification was performed using wheat germ agglutinin (WGA) assays, enzyme-linked immunosorbent assays, and real time-polymerase chain reaction. Endothelial barrier function was evaluated through measurements of transendothelial electrical resistance (TEER), and permeability for dextrans. Water flux across the endothelium was determined using the D2O dilution method.

HUVEC expressed a functional glycocalyx. Enzymatic glycocalyx degradation reduced barrier integrity. Bradykinin and serotonin did not affect glycocalyx integrity, while histamine reduced WGA binding. Bradykinin and histamine also decreased hyaluronidase activity. Barrier function analysis showed that glycocalyx degradation and compound exposure led to increased water permeability, with no additive effects on TEER and permeability.

Glycocalyx degradation increased endothelial permeability, with possible implication for edema development. Bradykinin and serotonin did not affect glycocalyx composition, but histamine reduced its integrity. Glycocalyx degradation led to a further increase in mediator-induced water permeability. This suggests a protective role of the glycocalyx endothelial dysfunction. This highlights its potential as a biomarker for angioedema.