%0 Journal Article
%T Circulating Endothelial Microvesicles Drive and Reflect Vascular Aging via miR-17-5p–Mediated Signaling
%A Hans Müller
%A Anna Schmidt
%A Thomas Weber
%J Interdisciplinary Research in Medical Sciences Specialty
%@ 3062-4401
%D 2025
%V 5
%N 1
%R 10.51847/6hOloGBwCF
%P 212-239
%X Vascular aging, defined by senescence and diminished functionality of brain endothelial cells (ECs), contributes importantly to multiple age-related cerebrovascular and neurodegenerative pathologies. Microvesicles (EMVs) and exosomes (EEXs) released by endothelial cells maintain the molecular characteristics of their parent cells and transport bioactive molecules capable of modulating recipient cell behavior. Nevertheless, the specific contributions of these vesicles to vascular aging processes remain incompletely understood. In this investigation, evaluations employing SA-β-gal staining, cerebral blood flow assessment, blood–brain barrier permeability, aging-associated molecular markers, and cognitive function testing demonstrated that EMVs secreted by young ECs provided superior attenuation of cerebrovascular and brain aging in mice compared with EEXs from the same cells. In contrast, EMVs originating from aged ECs promoted more pronounced aggravation of cerebrovascular and brain aging in mice than did EEXs released by aged ECs. Subsequent experiments established that these EMVs influence cerebrovascular and brain aging primarily through delivery of miR-17-5p and exert regulatory effects on EC senescence and activity via the miR-17-5p/PI3K/Akt signaling cascade. In older human subjects, circulating EMV abundance and EMV-associated miR-17-5p expression exhibited notable changes and displayed robust correlations with reactive oxygen species levels and vascular aging indices. Receiver operating characteristic curve analysis supported the utility of EMVs and EMV-miR-17-5p as potential diagnostic biomarkers of vascular aging. Overall, the results uncover previously unrecognized functions of EMVs, which exert more potent modulatory effects on vascular and brain aging than EEXs through control of EC behavior via the miR-17-5p/PI3K/Akt pathway. These findings further position EMVs and EMV-miR-17-5p as promising candidates for biomarkers and therapeutic intervention in vascular aging.
%U https://galaxypub.co/article/circulating-endothelial-microvesicles-drive-and-reflect-vascular-aging-via-mir-17-5pmediated-signal-tvovw8m1tenk5i8