Therapeutic effects of exosomes from angiotensin-converting enzyme 2 -overexpressed endothelial progenitor cells on intracerebral hemorrhagic stroke

Abstract

Objective: We have previously demonstrated that angiotensin-converting enzyme 2 (ACE2) could boost the therapeutic effects of endothelial progenitor cells (ACE2-EPCs) on stroke. However, where this effect comes from is still unclear. Here, we investigated whether the exosomes (EXs) released from ACE2-EPCs could provide the benefit for acute intracerebral hemorrhagic stroke (ICH). Methods: The C57BL/6 mice were induced ICH by collagenase injection, followed by intravenously administration of ACE2-EPC-EXs. ACE2 blocker, DX600 was used to verify the effects of ACE2. The neurological deficit score (NDS), hemorrhage volume, brain water content, and blood–brain barrier (BBB) permeability were measured at day 2 after injection. The levels of ACE2 and inflammatory factors/genes in the brain were also measured. Results: EPC-EXs decreased hemorrhage volume, brain edema, BBB permeability, and improved NDS, which were enhanced by ACE2-EPC-EXs treatment; 2) As compared to EPC-EXs, ACE2-EPC-EXs resulted in an up-regulation of ACE2 in the brain, associating with the down-regulated expressions of TNF-α and NFкB and up-regulated level of IκBα. 3) DX600 blocked the above mentioned protective effects of ACE2-EPC-EXs in ICH mice. Conclusion: These data suggest that the infusion of ACE2-EPC-EXs could provide the therapeutic effect on acute ICH by alleviating the post-stroke inflammation via transferring ACE2.

Keywords

• Intracerebral hemorrhage stroke
• Angiotensin-converting enzyme 2 (ACE2)
• Exosomes (EXs)
• Endothelial progenitor cells (EPCs)