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Fernandez-Bravo, S.

Publications and source records attributed to Fernandez-Bravo, S..

2 recordsLinked to original sources
bioRxiv2026

Circulating miR-29a as a new biomarker of food anaphylaxis and endothelial glycocalyx regulation

To the editorO_ST_ABSBackgroundC_ST_ABSAnaphylaxis is an acute and potentially life-threatening hypersensitivity reaction often involving the cardiovascular system. Circulating microRNAs (miRNAs/miR), including those carried by extracellular vesicles (EVs), are emerging biomarkers that display regulatory functions in allergy. This study aims to investigate the role of miR-29a in anaphylaxis. MethodsMiR-29a (3p and 5p) levels were assessed by qPCR from acute and baseline samples of serum and EVs from 70 patients with food- and drug-mediated anaphylaxis. EVs purification was confirmed by Western blot, electron microscopy, and NanoSight. MiR-29a-3p target genes were studied in silico using systems biology analysis (SBA). Moreover, miR-29a levels were evaluated in vitro in endothelial cells (ECs) exposed to anaphylactic mediators. Additionally, a panel of endothelial glycocalyx (eGCX)-associated mRNA was analyzed after transfection with a miR-29a-3p inhibitor. ResultsPatients with food-induced anaphylaxis exhibited reduced miR-29a-3p levels in both serum and EVs during the acute reaction. In contrast, miR-29a-5p levels were decreased in serum but not in EVs. No significant modulation of either miRNA was observed in drug-induced anaphylaxis. SBA of miR-29a-3p identified molecular pathways, biological processes and functional networks associated with eGCX remodelling. Intracellular levels of miR-29a-3p were modulated in vitro in ECs following exposure to anaphylactic mediators. Inhibition of miR-29a-3p significantly reduced ESM1 expression. ConclusionsThe miR-29a-3p levels are decreased in serum and EVs from patients with acute food-induced anaphylaxis, suggesting its potential as a promising biomarker. Moreover, a role for miR-29a-3p in eGCX integrity under anaphylactic conditions was demonstrated, potentially regulating ESM1. Key MessageMiR-29a-3p is selectively reduced in serum and extracellular vesicles during acute food-induced anaphylaxis and may regulate endothelial glycocalyx-related pathways, which supports its potential as a novel biomarker and molecular mediator of vascular involvement in anaphylactic reactions.

immunology↗
bioRxiv2025

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

BackgroundAnaphylaxis is an acute life-threatening reaction. Research into the vascular endothelium and its components may improve disease management and patient outcomes. ObjectiveWe investigated the endothelial glycocalyx (eGCX) and its pathophysiological role in murine anaphylaxis, aiming to identify novel diagnostic and therapeutic targets. MethodsActive 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. ResultsASA, 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. ConclusionseGCX shedding, particularly of ESM-1, acts as a key mediator in murine anaphylaxis. Sdx prophylaxis protects against severe reactions and improves survival. Clinical ImplicationTherapies based on glycosaminoglycans and proteoglycans may mitigate anaphylaxis severity, and monitoring eGCX dynamics could aid diagnosis. Capsule summaryEndothelial glycocalyx shedding contributes to anaphylaxis pathophysiology; targeting its preservation and measuring HA and ESM1 may offer novel diagnostic and therapeutic strategies for clinicians.

immunology↗