Plasma from Volunteers Breathing Helium Reduces Hypoxia-Induced Cell Damage in Human Endothelial Cells-Mechanisms of Remote Protection Against Hypoxia by Helium

Cardiovasc Drugs Ther. 2019 Jun;33(3):297-306. doi: 10.1007/s10557-019-06880-2.


Purpose: Remote ischemic preconditioning protects peripheral organs against prolonged ischemia/reperfusion injury via circulating protective factors. Preconditioning with helium protected healthy volunteers against postischemic endothelial dysfunction. We investigated whether plasma from helium-treated volunteers can protect human umbilical vein endothelial cells (HUVECs) against hypoxia in vitro through release of circulating of factors.

Methods: Healthy male volunteers inhaled heliox (79% helium, 21% oxygen) or air for 30 min. Plasma was collected at baseline, directly after inhalation, 6 h and 24 h after start of the experiment. HUVECs were incubated with either 5% or 10% of the plasma for 1 or 2 h and subjected to enzymatically induced hypoxia. Cell damage was measured by LDH content. Furthermore, caveolin 1 (Cav-1), hypoxia-inducible factor (HIF1α), extracellular signal-regulated kinase (ERK)1/2, signal transducer and activator of transcription (STAT3) and endothelial nitric oxide synthase (eNOS) were determined.

Results: Prehypoxic exposure to 10% plasma obtained 6 h after helium inhalation decreased hypoxia-induced cell damage in HUVEC. Cav-1 knockdown in HUVEC abolished this effect.

Conclusions: Plasma of healthy volunteers breathing helium protects HUVEC against hypoxic cell damage, possibly involving circulating Cav-1.

Keywords: Caveolin-1; Endothelial conditioning; Helium; Ischemic preconditioning; Remote.

MeSH terms

  • Administration, Inhalation
  • Adult
  • Caveolin 1 / genetics
  • Caveolin 1 / metabolism
  • Cell Hypoxia
  • Cells, Cultured
  • Healthy Volunteers
  • Helium / administration & dosage*
  • Human Umbilical Vein Endothelial Cells / metabolism*
  • Human Umbilical Vein Endothelial Cells / pathology
  • Humans
  • Male
  • Middle Aged
  • Oxygen / administration & dosage*
  • Plasma / metabolism*
  • Signal Transduction
  • Young Adult


  • CAV1 protein, human
  • Caveolin 1
  • Helium
  • heliox
  • Oxygen