Endothelial Dysfunction in Fabry Disease Is Related to Glycocalyx Degradation

Fabry disease (FD) is an X-linked multisystemic lysosomal storage disease due to a deficiency of α-galactosidase A ( /AGAL). Progressive cellular accumulation of the AGAL substrate globotriaosylceramide (Gb ) leads to endothelial dysfunction. Here, we analyzed endothelial function and in an AGAL-deficient genetic background to identify the processes underlying this small vessel disease. Arterial stiffness and endothelial function was prospectively measured in five males carrying variants (control) and 22 FD patients under therapy. AGAL-deficient endothelial cells (EA.hy926) and monocytes (THP1) were used to analyze endothelial glycocalyx structure, function, and underlying inflammatory signals. Glycocalyx thickness and small vessel function improved significantly over time (p