Distinct roles of glycocalyx components in regulating endothelial functions in a perfused three-dimensional human endothelium-on-a-chip
Issued Date
2026-01-01
Resource Type
ISSN
03636143
eISSN
15221563
Scopus ID
2-s2.0-105025656144
Pubmed ID
41285157
Journal Title
American Journal of Physiology Cell Physiology
Volume
330
Issue
1
Start Page
C129
End Page
C141
Rights Holder(s)
SCOPUS
Bibliographic Citation
American Journal of Physiology Cell Physiology Vol.330 No.1 (2026) , C129-C141
Suggested Citation
Tanawattanasuntorn T., Phungsom A., Muta K., Lokakaew J., Chotiwan N., Ketsawatsomkron P. Distinct roles of glycocalyx components in regulating endothelial functions in a perfused three-dimensional human endothelium-on-a-chip. American Journal of Physiology Cell Physiology Vol.330 No.1 (2026) , C129-C141. C141. doi:10.1152/ajpcell.00191.2025 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/114855
Title
Distinct roles of glycocalyx components in regulating endothelial functions in a perfused three-dimensional human endothelium-on-a-chip
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Corresponding Author(s)
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Abstract
Increased degradation of the endothelial glycocalyx (EGX) is associated with cardiovascular disease. However, whether EGX impairment drives endothelial dysfunction or reflects disease severity remains unclear. Prior studies investigating EGX function primarily used two-dimensional (2-D) endothelial cell cultures, which poorly mimic the endothelial microenvironment, particularly lacking luminal shear flow. To address these limitations, we leveraged a three-dimensional (3-D) human endothelium-on-a-chip to examine the roles of EGX components, namely heparan sulfate (HS) and sialic acid (SA), in regulating vascular permeability and monocyte adhesion. EGX expression was markedly higher in perfused 3-D human umbilical vein endothelial cells (HUVECs) cultures than in 2-D cultures. In 3-D HUVECs, tumor necrosis factor-alpha, a disruptor of endothelial function, did not reduce EGX expression, whereas dengue nonstructural protein 1 downregulated EGX. In 3-D HUVECs, HS degradation by heparinase III significantly increased endothelial permeability to 70-kDa fluorescein isothiocyanate-dextran without inducing cytotoxicity, whereas SA cleavage by neuraminidase reduced vascular permeability. Interestingly, neither HS nor SA cleavage affected 3-D human coronary artery endothelial cells (HCAECs) permeability. However, neuraminidase treatment significantly increased monocyte adhesion in both 3-D HUVECs and HCAECs, an effect not observed in heparinase III-treated 3-D endothelium from either vessel bed. These findings demonstrate that HS and SA play distinct roles in regulating endothelial barrier function and vascular inflammation in 3-D human endothelium.