Sex differences in circulating platelet-derived CD41+ extracellular vesicles in healthy adults

Extracellular vesicles (EVs) facilitate intercellular communication and reflect the physiological state of their parent cells. Microvesicles (MVs; ~200-900 nm) are released during cellular activation or stress and may provide insight into sex-related physiological differences. This study aimed to characterize circulating MV concentration, cellular origin, and MV microRNA cargo in healthy young males and females. Fasted sodium citrate plasma samples from healthy male (n = 16, age: 29 ± 6 years, BMI: 24.4 ± 2.4 kg/m²) and female (n = 16, age: 27 ± 5 years, BMI: 22.7 ± 1.9 kg/m²) participants were analyzed using size exclusion chromatography, tunable resistive pulse sensing, nano-flow cytometry, and RT-qPCR. MV concentration, antibody-defined MV subpopulations, and MV-miRNA cargo were assessed using linear models adjusted for age and BMI. Females exhibited higher concentrations of circulating platelet-derived CD41+ MVs (p = 0.03, d = 0.923), with a tendency for elevated monocyte-derived CD14+ MVs (p = 0.08, d = 0.546). No differences were observed for total MV concentration, remaining antibody-defined MV subpopulations, or MV-miRNA cargo expression. These findings demonstrate that healthy females exhibit elevated platelet- and monocyte-derived MV concentrations, while overall MV concentration and MV miRNA cargo are similar between sexes.