Extracellular Vesicles Derived from Intermittent Hypoxia–Treated Red Blood Cells Impair Endothelial Function Through Regulating eNOS Phosphorylation and ET-1 Expression

Quick Facts

  • Publication title: Extracellular Vesicles Derived from Intermittent Hypoxia–Treated Red Blood Cells Impair Endothelial Function Through Regulating eNOS Phosphorylation and ET-1 Expression
  • Journal: Cardiovasc Drug Ther
  • Year: 2020
  • DOI: 10.1007/s10557-020-07117-3
  • PMID/PMCID: 33242203; 27188535

Research overview

The aim of this research is to clarify whether and how EVs shedding from red blood cells (RBCs) are involved in IH-induced endothelial dysfunction. However, the underlying mechanism still remains unclear.

Key findings

Functional results demonstrated that REVs from OSA patients dramatically impaired endothelium-dependent relaxations (EDRs).

Similarly, in vivo and ex vivo studies showed that IH REVs caused significant endothelial dysfunction compared to control group.

Further results presented that IH REVs blocked endothelial nitric oxide synthase (eNOS) phosphorylation through inhibiting PI3K/Akt pathway and enhanced endothelin-1 (ET-1) expression through activating Erk1/2 pathway in endothelial cells.

Meanwhile, endothelial dysfunction caused by IH REVs was reversed by Akt activator SC79 as well as Erk kinase inhibitor PD98059, suggesting that PI3K/Akt/eNOS and Erk1/2/ET-1 pathways were implicated in IH REV-induced impaired EDRs.

Study design

EVs were extracted by ultracentrifugation.

After the identification of property and purity, EVs from IH-exposed RBCs (IH REVs) and normoxia-exposed RBCs (NOR REVs) or from OSA and non-OSA patient RBCs were utilized to treat C57BL/6 mouse aortas or human umbilical vein endothelial cells (HUVECs) for mechanistic exploration.

Echo Biotech Role

Echo Biotech contributed EV characterization.

Related platforms: Exoomics®

Related services and capabilities: EV Basic Characterization (TEM/NTA/WB)

References

Original publication: Extracellular Vesicles Derived from Intermittent Hypoxia–Treated Red Blood Cells Impair Endothelial Function Through Regulating eNOS Phosphorylation and ET-1 Expression Cardiovasc Drug Ther. 2020. DOI: 10.1007/s10557-020-07117-3. PMID/PMCID: 33242203; 27188535.