Multiparametric Extracellular Vesicle Profiling Identifies a Distinct Circulating Signature of Bicuspid Aortic Valve Disease

Patients with bicuspid aortic valve disease show fundamentally altered circulating large extracellular vesicle (LEV) profiles versus tricuspid aortic valve disease, including a distinct neutrophil-associated signature.

• Why it matters: Bicuspid aortic valves develop calcific aortic valve disease earlier and progress faster, but circulating molecular drivers are poorly defined. EVs could reveal morphology-specific pathophysiology.
• What they did: The study quantified LEV abundance and morphology using single-vesicle nano-flow cytometry and super-resolution microscopy, then used proteomic profiling to compare LEV cargoes between BAV and TAV. It also assessed platelet- and leukocyte-associated adhesion molecule microdomains and linked LEV populations to clinical parameters.
• The result: Super-resolution imaging showed BAV-specific EV membrane microdomains organizing platelet- and leukocyte-associated adhesion molecules, and proteomics identified a BAV-specific neutrophil-associated cargo enrichment tied to neutrophil degranulation and innate immunity. LEV populations in BAV also differed in platelet- and neutrophil-associated fractions, and LEV–clinical parameter associations suggested morphology-linked disease severity.

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