Effects of Endothelial Progenitor Cell-Derived Microvesicles on HypoxiaReoxygenation-Induced Endothelial Dysfunction and Apoptosis

Abstract EN

Oxidative stress-induced endothelial dysfunction plays a key role in ischemia/reperfusion injury.

Recent evidence indicates that endothelial progenitor cell-derived microvesicles (EPC-MVs) can promote angiogenesis of endothelial cells (ECs).

Here, we investigated the potential effects of EPC-MVs on hypoxia/reoxygenation (H/R) injury in human brain microvascular ECs (hb-ECs).

MVs were prepared from EPCs cultured in a serum deprivation (SD) medium (starving stress, sEPC-MVs) or SD medium containing tumor necrosis factor-α (TNFα) (apoptotic stress, aEPC-MVs).

H/R injury model of hb-ECs was produced by 6 hr hypoxia (1% O2) and 24 hr reoxygenation.

The H/R hb-ECs were co-cultured with EPC-MVs.

Results showed that (1) H/R hb-ECs were dysfunctional and coupled with increased apoptosis and ROS overproduction; (2) under two different conditions, EPCs displayed remarkable difference in caspase 3 and miR126 expression, which were carried by the corresponsive EPC-MVs; (3) functionally, sEPC-MVs had beneficial effects on H/R hb-ECs, whereas aEPC-MVs had detrimental effects; (4) the diverse effects of sEPC-MVs and aEPC-MVs were associated with the changes in miR126 and eNOS expression and were abolished by PI3K inhibitor.

In conclusion, sEPCs-MVs and aEPC-MVs are functionally different on hb-EC apoptosis and dysfunction via their carried RNAs associated with ROS production and PI3K/eNOS/NO pathway.