Investigation of plasma-derived extracellular vesicles in hypertrophic cardiomyopathy patients

Hypertrophic cardiomyopathy (HCM) is a genetically determined heart disease characterized by marked clinical heterogeneity and limited availability of specific circulating biomarkers that reflect underlying disease mechanisms. This study investigated whether plasma-derived extracellular vesicles (EVs) capture disease-related molecular features in patients with HCM. Plasma EVs were characterized for size, cellular origin, and protein cargo using flow cytometry and targeted and untargeted proteomic analyses. While size and concentration of EVs were comparable between groups, patients with HCM exhibited an enrichment of platelet-derived EVs (CD41a⁺) and reductions in neutrophil (CD66b⁺)- and lymphatic-endothelial-cell (CD310⁺)-derived EVs. Proteomic profiling revealed EV-associated proteins linked to platelet activation and thrombo-inflammation. Multivariable protein signatures derived from EVs discriminated patients from controls with performance comparable to plasma-based models and were not influenced by age. These findings indicate that plasma-derived EVs capture key biological pathways involved in HCM and may complement biomarker discovery strategies.