Endothelial extracellular vesicles containing miR-126-5p and miR-212-3p initiate monocyte activation and vascular inflammation following radiation exposure in vitro and in vivo.
Does radiation exposure induce vascular inflammation via endothelial EV-derived miR-126-5p and miR-212-3p in preclinical models?
Endothelial EV-derived miR-126-5p and miR-212-3p mediate monocyte activation in radiation-induced vascular inflammation, suggesting their potential as biomarkers for radiation-induced atherosclerosis.
People exposed to radiation in cancer therapy and nuclear accidents are at increased risk of cardiovascular outcomes in long-term survivors. Extracellular vesicles (EVs) are involved in radiation-induced endothelial dysfunction, but their role in the early stage of vascular inflammation after radiation exposure remains to be fully understood. Herein, we demonstrate that endothelial cell-derived EVs containing miRNAs initiate monocyte activation in radiation-induced vascular inflammation. In vitro co-culture and in vivo experimental data showed that endothelial EVs can be sensitively increased by radiation exposure in a dose-dependent manner, and stimulate monocytes releasing monocytic EVs and adhesion to endothelial cells together with an increase in the expression of genes encoding specific ligands for cell-cell interaction. Small RNA sequencing and transfection using mimics and inhibitors explained that miR-126-5p and miR-212-3p enriched in endothelial EVs initiate vascular inflammation by monocyte activation after radiation exposure. Moreover, miR-126-5p could be detected in the circulating endothelial EVs of radiation-induced atherosclerosis model mice, which was found to be tightly correlated with the atherogenic index of plasma. In summary, our study showed that miR-126-5p and miR-212-3p present in the endothelial EVs mediate the inflammatory signals to activate monocytes in radiation-induced vascular injury. A better understanding of the circulating endothelial EVs content can promote their use as diagnostic and prognostic biomarkers for atherosclerosis after radiation exposure.
Choi et al. (Mon,) conducted a other in Radiation-induced vascular inflammation and atherosclerosis. Radiation exposure was evaluated on Monocyte activation and vascular inflammation. Endothelial extracellular vesicles containing miR-126-5p and miR-212-3p initiate monocyte activation and vascular inflammation following radiation exposure in vitro and in vivo.