The miR‐126‐5p and miR‐212‐3p in the extracellular vesicles activate monocytes in the early stage of radiation‐induced vascular inflammation implicated in atherosclerosis

Abstract

Abstract 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.

Keywords

• endothelium
• extracellular vesicle
• miRNAs
• monocytes
• radiation exposure