Acrolein-mediated carbonylation of proheparanase-1 drives endothelial glycocalyx degradation in human immortalized brain microvascular endothelial cells

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ID: 322618
2026
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Abstract
The endothelial glycocalyx plays a pivotal role in maintaining blood-brain barrier integrity, and its degradation promotes leukocyte adhesion and transendothelial migration. We previously reported that the degradation of heparan sulfate (HS), a major structural component of the glycocalyx, aggravated inflammation after stroke onset. In addition, acrolein (ACR), an α,β-unsaturated aldehyde generated following stroke onset, promoted HS degradation via activation of proheparanase-1 (proHPSE1), the inactive precursor of heparanase-1 (HPSE1). However, whether this ACR-mediated HS degradation occurs in a cell-type specific manner and contributes to endothelial glycocalyx dysfunction, particularly by enhancing leukocyte adhesion, remains unclear. In this study, we demonstrated that ACR-mediated HS degradation promotes THP-1 cell adhesion to human immortalized brain microvascular endothelial cells (HBMEC/ci18). Immunochemical staining indicated that proHPSE1 was visualized on both HBMEC/ci18 and EA.hy926 cells. However, HS localization in HBMEC/ci18 cells differed from that in EA.hy926 cells, which may underlie the differential response of ACR-dependent HS degradation. Furthermore, supplementation of proHPSE1 containing ACR-carbonylated lysine residues directly induced HS degradation in HBMEC/ci18 cells. These results suggest that monocyte adhesion following glycocalyx degradation may be triggered by ACR-induced carbonylation of proHPSE1 during brain infarction. HBMEC/ci18 cells exposed to ACR or treated with carbonylated proHPSE1 provide a useful model for screening agents that protect the endothelial glycocalyx.
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Authors Shizuno Matsuda, Masahiro Komeno, M Morishita, 朱莉 篠, Jia Shvi, Momo Shimekake, Kaho Kurano, Tomomi Furihata, Nobuaki Higashi, Itsuko Ishii, Toshihiko Toida, Kazuei Igarashi, Kyohei Higashi
Journal glycobiology
Year 2026
DOI
10.1093/glycob/cwag056
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