Biology subjects

Esteban, V.

Publications and source records attributed to Esteban, V..

4 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↗

bioRxiv2026

The transcription factor NF-Y promotes myeloid cell survival and protects from inflammatory vascular disease

BackgroundMyeloid cells orchestrate vascular inflammation through transcriptional programs that regulate their maturation, effector function, and survival. While lineage-determining transcription factors establish myeloid identity, understanding of the transcriptional regulation of myeloid behavior in chronic inflammatory contexts remains limited. Nuclear factor-Y (NF-Y) is a trimeric CCAAT-binding transcription factor that regulates cell proliferation and differentiation. Here, we investigate the role of NF-Y in myeloid function and survival during chronic vascular inflammation. MethodsIntegrated single-cell transcriptomics of BM, blood, and atherosclerotic lesions were combined with myeloid-specific NF-YA inactivation to define NF-Y-dependent transcriptional states. Functional consequences were assessed in mice with myeloid-specific Nfya deletion on a hypercholesterolemic Apoe-/- background using models of diet-induced advanced atherosclerosis and endoluminal femoral injury. Myeloid cell recruitment, survival, apoptosis, and proliferation were further examined in models of thioglycolate-induced peritonitis. ResultsNF-Y subunit transcripts were detected across myeloid compartments, with Nfya enriched in proliferative macrophages and immature neutrophils. In mouse atherosclerotic lesions, low Nfya expression was associated with lipid-handling and phagocytic macrophage signatures and a pro-inflammatory neutrophil phenotype. Myeloid Nfya deficiency was further associated with reduced circulating neutrophil counts, increased macrophage and neutrophil apoptosis during acute inflammation, expanded necrotic cores, larger unstable atherosclerotic lesions, and aggravated atherosclerosis and injury-induced neointimal thickening. ConclusionOur data identify NF-Y as a transcriptional safeguard of myeloid cell survival during inflammatory stress, thereby shaping disease progression and outcomes in vascular disease.

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↗

bioRxiv2023

Allergic inflammation triggers dyslipidemia via IgG signalling

BackgroundAllergic diseases begin early in life and are often chronic, thus creating an inflammatory environment that may precede or exacerbate other pathologies. In this regard, allergy has been associated to metabolic disorders and with a higher risk of cardiovascular disease, but the underlying mechanisms remain incompletely understood. MethodsWe used a murine model of allergy and atherosclerosis, different diets and sensitization methods, and cell-depleting strategies to ascertain the contribution of acute and late phase inflammation to dyslipidemia. Untargeted lipidomic analyses were applied to define the lipid fingerprint of allergic inflammation at different phases of allergic pathology. Expression of genes related to lipid metabolism was assessed in liver and adipose tissue at different times post-allergen challenge. Also, changes in serum triglycerides (TG) were evaluated in a group of 59 patients [≥]14 days after the onset of an allergic reaction. ResultsWe found that allergic inflammation induces a unique lipid signature that is characterized by increased serum TG and changes in the expression of genes related to lipid metabolism in liver and adipose tissue. Alterations in blood TGs following an allergic reaction are independent of T-cell-driven late phase inflammation. On the contrary, the IgG-mediated alternative pathway of anaphylaxis is sufficient to induce a TG increase and a unique lipid profile. Lastly, we demonstrated an increase in serum TG in 59 patients after undergoing an allergic reaction. ConclusionOverall, this study reveals that IgG-mediated allergic inflammation regulates lipid metabolism.

immunology↗