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The selective sorting of microRNA-4432 into endothelial extracellular vesicles is controlled by a specific RNA binding protein: new insights into the pathophysiology of venous malformations

Year: 2025

Type: article

Abstract: Venous malformations (VMs) are among the most common congenital vascular anomalies, characterized by slow blood flow and resulting from vascular dysgenesis.1,2 These anomalies frequently present in the head and neck region and can progressively enlarge, leading to symptoms ranging from cosmetic deformities to severe, life-threatening complications such as airway obstruction. Current treatment options, including sclerotherapy and surgical resection, are limited by their invasive nature and high recurrence rates.3,4 Mutations in endothelial cells (ECs) are known to drive atypical cytological behaviour in VMs, with the construction of perivascular structures being mediated by molecular signals originating from these intrinsic endothelial mutations.5,6 Histopathologically, VMs exhibit a disorganized and discontinuous endothelium, sparse perivascular cells, and an irregular extracellular matrix.7 Genetically, most VMs are associated with mutations in the TEK gene, which encodes the endothelial tyrosine kinase receptor TIE2. Mutations such as L914F and R849W lead to ligand-independent activation of TIE2, triggering downstream activation of the PI3 K/AKT signalling cascade.1 These mutations disrupt the production of critical signalling molecules, including transforming growth factor-β and platelet-derived growth factor-B, which are essential for recruiting and maintaining perivascular cells. Dysfunction in TIE2-mutant ECs has been demonstrated to induce VM lesions in experimental models, underscoring their central role in VM pathogenesis.

Source: British Journal of Dermatology

DOI: 10.1093/bjd/ljaf033

Authors: Stanislovas S Jankauskas, Fahimeh Varzideh, Emanuele Farroni, Pasquale Mone, Urna Kansakar, Gaetano Santulli

Institutions: Albert Einstein College of Medicine, University of Molise, Federico II University Hospital, University of Naples Federico II

Language: English

Topic: Extracellular vesicles in disease

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green