Effects of Endothelial Progenitor Cell-Derived Microvesicles on Hypoxia/Reoxygenation-Induced Endothelial Dysfunction and Apoptosis

Abstract

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.

Therapeutic effects of mesenchymal stem cell-derived microvesicles on pulmonary arterial hypertension in rats

“…We found that endothelial progenitor cell-MVs could protect endothelial cells against hypoxia-induced injury in in vitro culture systems [11] . Furthermore, a recent study indicated that MSC-MVs acquire the function of MSCs and can inhibit vascular remodeling and hypoxic pulmonary hypertension in a hypoxia-induced pulmonary hypertension mouse model [12] , indicating a novel application for stem cell-based therapy.…”

Loading MiR-210 in Endothelial Progenitor Cells Derived Exosomes Boosts Their Beneficial Effects on Hypoxia/Reoxygeneation-Injured Human Endothelial Cells via Protecting Mitochondrial Function

“…EPC-derived microvesicles can protect kidneys from ischemia/reperfusion injury [7] and improve neovascularization in a murine model of hindlimb ischemia through their shuttled microRNAs (miRs), miR-126 and miR-296 [8]. Our group has demonstrated that EPC-released extracellular vesicles could protect ECs against hypoxia/reoxygenation (H/R) injury, which is at least in part mediated by their carried miR-126 [9].…”

Microparticles in kidney diseases: focus on kidney transplantation

“…These functional roles might rely on the orchestrated mechanisms associated with MV-carried ribonucleic acids (RNAs) in control of reactive oxygen species (ROS) production and phosphatidylinositol-3 kinase/ endothelial nitric oxide synthase/nitric oxide (PI3K/ eNOS/NO) pathway in the target cells. These findings indicate that EPC-MVs could be used as a novel vehicle for treating H/R injury [50].…”