Endothelial derived microvesicles modulate cerebrovascular and brain aging via MiR‐17‐5p and the biomarker potential in vascular aging

Abstract Vascular aging, which is marked by brain endothelial cell (EC) senescence and functional impairment, plays a significant role in diverse age‐related cerebrovascular and neurodegenerative disorders. EC‐derived microvesicles (EMVs) and exosomes (EEXs) preserve the molecular signatures of their source cells and deliver bioactive cargo to regulate the activity of target cells, but their potentials in vascular aging remain unclear. Here, as indicated by SA‐β‐gal staining, cerebral blood flow, blood brain barrier function, aging related markers and cognitive ability test, we found that young ECs released EMVs could more effectively alleviate mice cerebrovascular and brain aging than EEXs. Aged ECs released EMVs were more effective than their released EEXs on aggravating mice cerebrovascular and brain aging. We further identified that these EMVs regulated cerebrovascular and brain aging by transferring miR‐17‐5p and could modulate ECs senescence and functions via miR‐17‐5p/PI3K/Akt pathway. Plasma EMV concentrations and EMV‐miR‐17‐5p expression were altered in older adults, showing strong associations with reactive oxygen species and vascular aging. Receiver operating characteristic analysis demonstrated the potential of EMVs and EMV‐miR‐17‐5p as diagnostic biomarkers for vascular aging. Our results revealed the novel roles for EMVs that could more effectively modulate vascular and brain aging than EEXs by regulating ECs functions through miR‐17‐5p/PI3K/Akt pathway, and also suggested that EMVs and EMV‐miR‐17‐5p represent promising biomarkers and therapeutic targets for vascular aging.