Extracellular vesicles in type 2 diabetes exhibit elevated miR-155 cargo and Annexin A1 concentration

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AIMS: Extracellular vesicles (EVs) facilitate intercellular communication and reflect cellular phenotypes. Large-sized EVs (200-1000 nm), commonly referred to as microvesicles (MVs), are released during cellular activation or apoptosis and may serve as biomarkers in chronic disease. The present study aimed to characterize circulating MV concentration, cellular origin, and miRNA cargo in individuals with type 2 diabetes (T2D) compared with healthy controls. MATERIALS AND METHODS: Fasted sodium citrate plasma samples from 36 individuals (T2D: n = 17; controls: n = 19; age-matched) were analyzed using size exclusion chromatography (SEC), nano-flow cytometry, tunable resistive pulse sensing (TRPS), and reverse transcription polymerase chain reaction (RT-PCR). MV concentration, antibody-defined MV subpopulations, and MV-associated miRNA cargo were assessed. Statistical analyses were performed using linear models adjusted for age, sex, and body mass index. KEY FINDINGS: Individuals with T2D exhibited significantly higher total MV concentrations and increased circulating CD14+/CD16-, CD16+/CD14-, CD31+/CD41-/CD62E+, CD41+, Annexin A5+, and Annexin A1+ MVs (all p < 0.038). MV-associated miR-155-5p expression was elevated in participants with T2D (p = 0.016). No group differences were observed for CD3+ or CD45+ MVs, nor for MV-associated miR-126-3p, miR-146a-5p, or miR-181b-5p. SIGNIFICANCE: These findings demonstrate that individuals with T2D exhibit elevated circulating MV concentrations and distinct distributions of specific MV subpopulations, alongside altered MV-associated miRNA cargo. The functional relevance of these MV-associated alterations warrants further investigation. NEW & NOTEWORTHY: Extracellular vesicles (EVs) are released by cells and are hypothesized to play important roles in inter-cellular communication while carrying signatures reflective of their origin cell. Our findings demonstrate that circulating EVs ~200-1000 nm in diameter are elevated in people living with T2D and exhibit distinct phenotypic and miRNA cargo profiles compared with healthy controls. These observations highlight the potential utility of circulating EVs as informative biomarkers of altered cellular states in T2D.

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