Extracellular vesicles (EV) mediate intercellular communication by carrying proteins, lipids, and nucleic acids. Recent research highlights their potential role in modulating neuro/cardiac physiology and pathology. Previously, we reported increased levels of astrocyte-derived EVs (ADEs) in plasma of women with HIV (WWH). Moreover, levels of astrocytic activation marker GFAP positively correlated with reactive oxygen species (ROS) in ADEs from WWH presenting cognitive impairment (CI).

Total exosomes were isolated from plasma of PWH by ultracentrifugation. ADEs were subsequently purified from total exosomes via immunoprecipitation of GLAST-1–positive EVs. Human AC16 cardiomyocytes were cultured and treated with varying concentrations of plasma-derived ADEs (10, 20, and 30 µg) for 24 hours. Oxidative stress and cell loss were assessed by immunocytochemistry and immunofluorescence microscopy through measurement of inducible nitric oxide synthase (iNOS) expression and quantification of DAPI-positive nuclei, respectively. All iNOS fluorescence intensity values were normalized to nuclear counts (sum intensity per nucleus).

Cardiomyocytes exposed to ADEs showed a clear dose-dependent increase in both iNOS expression and cell loss compared to unexposed cardiomyocytes.

These results indicate that ADEs from PWH induce cardiomyocyte oxidative stress and cell loss.  Further molecular profiling of ADEs cargo is needed to define the mechanisms involved and evaluate their physiological relevance. These findings highlight the potential impact of brain-derived EVs in heart physiology and pathology.