Cyclic hypoxia conditioning alters the content of myoblast-derived extracellular vesicles and enhances their cell-protective functions

Yan Yan, Tingting Gu, Stine Duelund Kaas Christensen, Junyi Su, Thomas Ravn Lassen, Marie Vognstoft Hjortbak, Iju Lo, Susanne Trillingsgaard Venø, Andrea Erzsebet Tóth, Ping Song, Morten Schallburg Nielsen, Hans Erik Bøtker, Blagoy Blagoev, Kim Ryun Drasbek, Jørgen Kjems*

*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Abstract

Remote ischemic conditioning (RIC) is a procedure that can attenuate ischemic-reperfusion injury by conducting brief cycles of ischemia and reperfusion in the arm or leg. Extracellular vesicles (EVs) circulating in the bloodstream can release their content into recipient cells to confer protective function on ischemia-reperfusion injured (IRI) organs. Skeletal muscle cells are potential candidates to release EVs as a protective signal during RIC. In this study, we used C2C12 cells as a model system and performed cyclic hypoxia-reoxygenation (HR) to mimic RIC. EVs were collected and subjected to small RNA profiling and proteomics. HR induced a distinct shift in the miRNA profile and protein content in EVs. HR EV treatment restored cell viability, dampened inflammation, and enhanced tube formation in in vitro assays. In vivo, HR EVs showed increased accumulation in the ischemic brain compared to EVs secreted from normoxic culture (N EVs) in a mouse undergoing transient middle cerebral artery occlusion (tMCAO). We conclude that HR conditioning changes the miRNA and protein profile in EVs released by C2C12 cells and enhances the protective signal in the EVs to recipient cells in vitro.

Original languageEnglish
Article number1211
JournalBiomedicines
Volume9
Issue9
Number of pages20
ISSN2227-9059
DOIs
Publication statusPublished - Sept 2021

Keywords

  • Cyclic hypoxia-reoxygenation
  • Extracellular vesicles
  • MicroRNAs
  • Myoblast
  • Proteins
  • Remote ischemic conditioning

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