Plasma-Derived Extracellular Vesicles Inhibit Lipopolysaccharide-Induced Apoptosis and Oxidative Stress in Human AC16 Cardiomyocytes.

Sepsis is frequently accompanied by myocardial dysfunction, which significantly worsens clinical outcomes. Lipopolysaccharide (LPS), a key component of Gram-negative bacteria, induces excessive oxidative stress and apoptosis in cardiomyocytes, contributing to sepsis-associated cardiac injury. Plasma-derived extracellular vesicles (EVs) have emerged as important mediators of intercellular communication and cardiovascular protection; however, their role in LPS-induced cardiomyocyte injury remains unclear. In this study, human AC16 cardiomyocytes were exposed to LPS in the presence or absence of plasma-derived EVs. Intracellular reactive oxygen species (ROS) production and apoptosis were assessed by flow cytometry, while apoptosis-related proteins and NF-κB signaling components were analyzed by Western blotting. The involvement of NF-κB signaling was further examined using pharmacological rescue experiments. Our results demonstrate that EV treatment markedly attenuated LPS-induced ROS accumulation and cardiomyocyte apoptosis. These protective effects were associated with reduced phosphorylation of NF-κB p65 and IκBα, as well as inhibition of p65 nuclear translocation. Notably, activation of NF-κB signaling abolished the anti-apoptotic and antioxidative effects of EVs under LPS challenge. Collectively, these findings suggest that plasma-derived EVs mitigate LPS-induced oxidative stress and apoptosis in human cardiomyocytes, potentially through modulation of NF-κB signaling. This study provides molecular insights into the cardioprotective actions of EVs and supports their potential as therapeutic candidates for sepsis-associated cardiovascular dysfunction.