Effects of hypoxic-ischemic pre-treatment on microvesicles derived from endothelial progenitor cells
Wen Zeng1, Qiaoling Lei1, Jiao Ma1
1Department of Neonatology, Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan 611731, P.R. China.
Abstract:
Endothelial progenitor cells (EPCs) have protective roles in ischemic injury due to their ability to improve endothelial function and modulate angiogenesis. Microvesicles (MVs) are small membrane particles released by various cell types, including EPCs, which affect various target cells by transferring carried genetic information, including microRNAs (miRNAs/miRs). Depending on the stimuli and cell types, MVs exert different functions. In the present study, oxygen-glucose deprivation (OGD) was used to mimic ischemic-hypoxic (HI) insult, where the effects of HI insult on EPC-derived MVs (EPC-MVs) were subsequently investigated. OGD induced Ca2+ influx in EPCs and increased the release of EPC-MVs compared with normoxic conditions. In addition, MVs prepared from EPCs cultured under normoxic conditions or OGD conditions (OGD-EMVs) had the ability to stimulate the proliferation of EPCs. Furthermore, OGD-EMVs induced stronger effects on proliferation, which may be associated with the upregulation of miR-210 in EPC-MVs. In conclusion, the present results indicated that HI insult promoted the release of MVs from EPCs and upregulated miR-210 in MVs, leading to positive modulation of the proliferation of EPCs cultured under normoxic conditions.
Insights
Ischemic-hypoxic insult enhances the release of microvesicles (MVs) from endothelial progenitor cells (EPCs). These MVs, particularly those from stressed EPCs, promote EPC proliferation, partly via increased miR-210 levels.
Area of Science:
- Cell Biology
- Regenerative Medicine
- Cardiovascular Research
Background:
- Endothelial progenitor cells (EPCs) are crucial for repairing ischemic injury by enhancing endothelial function and promoting angiogenesis.
- Microvesicles (MVs) released by cells, including EPCs, carry genetic material like microRNAs (miRNAs) and influence target cells.
- The function of EPC-derived MVs (EPC-MVs) can vary depending on cellular stimuli.
Purpose of the Study:
- To investigate the impact of ischemic-hypoxic (HI) insult on EPC-MVs.
- To determine how HI insult affects the release and function of EPC-MVs.
- To explore the role of specific miRNAs, such as miR-210, in mediating the effects of OGD-EMVs.
Main Methods:
- Mimicking ischemic-hypoxic (HI) insult using oxygen-glucose deprivation (OGD) in EPC cultures.
- Quantifying EPC-MV release under normoxic versus OGD conditions.
- Assessing the proliferative effects of EPC-MVs derived from normoxic and OGD-treated EPCs on normoxic EPCs.
- Analyzing miRNA content, specifically miR-210, in EPC-MVs.
Main Results:
- OGD induced calcium influx in EPCs and significantly increased EPC-MV release compared to normoxic conditions.
- Both normoxic and OGD-derived EPC-MVs stimulated EPC proliferation.
- EPC-MVs derived from OGD-treated EPCs (OGD-EMVs) exhibited a stronger proliferative effect.
- Upregulation of miR-210 was observed in EPC-MVs under OGD conditions, potentially contributing to the enhanced proliferation.
Conclusions:
- HI insult promotes the release of EPC-MVs.
- miR-210 is upregulated in EPC-MVs following HI insult.
- EPC-MVs, especially those released under stress, can positively modulate EPC proliferation, suggesting a role in endogenous repair mechanisms.
