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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 \u03b1,\u03b2-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). Immunocytochemistry 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.<\/jats:p>","DOI":"10.1093\/glycob\/cwag056","type":"journal-article","created":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T11:39:51Z","timestamp":1784893191000},"source":"Crossref","is-referenced-by-count":0,"title":["Acrolein-mediated carbonylation of proheparanase-1 drives endothelial glycocalyx degradation in human immortalized brain microvascular endothelial cells"],"prefix":"10.1093","volume":"36","author":[{"given":"Shizuno","family":"Matsuda","sequence":"first","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, Tokyo University of Science , 6-3-1 Niijyuku, Katsushika, Tokyo 125-8585 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Komeno","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, Tokyo University of Science , 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