Attenuation of endothelial glycocalyx shedding and endocan modulation by Sulodexide in murine models of anaphylaxis.

Background: Anaphylaxis is an acute life-threatening reaction. Research into the vascular endothelium and its components may improve disease management and patient outcomes. Objective: We investigated the endothelial glycocalyx (eGCX) and its pathophysiological role in murine anaphylaxis, aiming to identify novel diagnostic and therapeutic targets. Methods: Active systemic anaphylaxis (ASA) and passive systemic anaphylaxis (IgE-PSA and IgG1-PSA) models were evaluated in mice. Sulodexide (Sdx) was administered as a prophylactic treatment. eGCX structure and N-acetylglucosamine residues in mouse aortic tissue were analyzed by electron microscopy and wheat germ agglutinin (WGA) staining. Endocan (ESM-1) levels in mouse aorta and plasma were determined by immunofluorescence and ELISA. Human sera from beta-lactam-induced anaphylaxis and endothelial cell (EC) secretome samples were also analyzed. Results: ASA, IgE-PSA, and IgG1-PSA models showed reduced eGCX surface area and thickness. N-acetylglucosamine and ESM-1 levels decreased in aortic tissue but increased in plasma, indicating glycocalyx shedding. Consistently, ESM-1 secretion was enhanced in ECs exposed to acute anaphylactic sera. ESM-1 and hyaluronic acid levels differed significantly between anaphylactic patients and non-allergic controls. Sdx reduced reaction severity in ASA and IgE-PSA, increased survival in ASA, and prevented eGCX disruption and ESM-1 release. Conclusions: eGCX shedding, particularly of ESM-1, acts as a key mediator in murine anaphylaxis. Sdx prophylaxis protects against severe reactions and improves survival. Clinical Implication: Therapies based on glycosaminoglycans and proteoglycans may mitigate anaphylaxis severity, and monitoring eGCX dynamics could aid diagnosis.