Streptococcus mutans-derived extracellular vesicles disrupt endothelial function via eNOS and endothelin-1 modulation.

Epidemiological research has identified links between dental caries and cardiovascular diseases, yet the underlying mechanisms remain insufficiently elucidated. Given the pivotal role of endothelial dysfunction in cardiovascular diseases, the cariogenic pathogen Streptococcus mutans (S.m), and the significance of bacterial extracellular vesicles (EVs) in host-microbe interactions, we investigated the impact of S.m-derived extracellular vesicles (S.m EVs) on endothelial function. Oral administration of S.m was found to impair endothelial-dependent relaxation (EDR) in vivo. Isolated S.m EVs directly lead to diminished EDR in a dose- and time-dependent manner. Mechanistically, S.m EVs inhibited Akt and eNOS phosphorylation while promoting p38 MAPK phosphorylation and endothelin-1 expression. Further study demonstrates that the Akt/eNOS pathway and the p38 MAPK/endothelin-1axis were involved in S.m EVs-impaired endothelial function. These findings reveal the adverse effects and mechanisms of S.m EVs on endothelial function, establishing a mechanistic link between caries and cardiovascular diseases.