Heparan sulfate (pulmonary endothelial glycocalyx) (HS)

Heparan sulfate (HS) is a complex, highly sulfated linear polysaccharide that serves as the primary functional component of the endothelial glycocalyx, a carbohydrate-rich layer lining the pulmonary vasculature. In the lungs, HS is critical for maintaining the alveolar-capillary barrier, sensing fluid shear stress, and regulating the recruitment of inflammatory cells by sequestering chemokines and cytokines (Schmidt et al., 2012, Nature Medicine). Under pathological conditions such as sepsis or ARDS, HS undergoes "disease-modification," which involves enzymatic cleavage by heparanase and structural alterations in sulfation patterns, leading to glycocalyx shedding and catastrophic vascular leakage (Iba et al., 2019, Journal of Intensive Care). From a therapeutic perspective, these disease-modified HS variants represent both a biomarker of endothelial injury and a target for vascular stabilization. Strategies include the use of heparanase inhibitors to prevent HS degradation and the administration of HS mimetics or stabilizers like sulodexide to restore the protective glycocalyx architecture (Zhang et al., 2021, Frontiers in Cell and Developmental Biology). Protecting pulmonary HS is increasingly recognized as a vital approach to treating acute lung injury and preventing the progression of multi-organ failure in critically ill patients (Uchimido et al., 2019, Journal of Intensive Care).

Other names

Endothelial heparan sulfateHeparan sulfate proteoglycan (HSPG) fragmentsDisease-modified heparan sulfatePulmonary vascular glycocalyx HSShed heparan sulfate

Inhibition of heparanase-mediated degradation of the glycocalyx, competitive binding to pro-inflammatory cytokines/chemokines, and pharmacological stabilization or replenishment of the endothelial surface layer to restore vascular barrier function.