Near-infrared II photobiomodulation augments nitric oxide bioavailability via phosphorylation of endothelial nitric oxide synthase

FASEB J. 2022 Sep;36(9):e22490. doi: 10.1096/fj.202101890R.


There is solid evidence of the beneficial effect of photobiomodulation (PBM) with low-power near-infrared (NIR) light in the NIR-I window in increasing bioavailable nitric oxide (NO). However, it is not established whether this effect can be extended to NIR-II light, limiting broader applications of this therapeutic modality. Since we have demonstrated PBM with NIR laser in the NIR-II window, we determined the causal relationship between NIR-II irradiation and its specific biological effects on NO bioavailability. We analyzed the impact of NIR-II irradiation on NO release in cultured human endothelial cells using a NO-sensitive fluorescence probe and single-cell live imaging. Two distinct wavelengths of NIR-II laser (1064 and 1270 nm) and NIR-I (808 nm) at an irradiance of 10 mW/cm2 induced NO release from endothelial cells. These lasers also enhanced Akt phosphorylation at Ser 473, endothelial nitric oxide synthase (eNOS) phosphorylation at Ser 1177, and endothelial cell migration. Moreover, the NO release and phosphorylation of eNOS were abolished by inhibiting mitochondrial respiration, suggesting that Akt activation caused by NIR-II laser exposure involves mitochondrial retrograde signaling. Other inhibitors that inhibit known Akt activation pathways, including a specific inhibitor of PI3K, Src family PKC, did not affect this response. These two wavelengths of NIR-II laser induced no appreciable NO generation in cultured neuronal cells expressing neuronal NOS (nNOS). In short, NIR-II laser enhances bioavailable NO in endothelial cells. Since a hallmark of endothelial dysfunction is suppressed eNOS with concomitant NO deficiency, NIR-II laser technology could be broadly used to restore endothelial NO and treat or prevent cardiovascular diseases.

Keywords: endothelial nitric oxide synthase; near-infrared II; nitric oxide; photobiomodulation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Cells, Cultured
  • Endothelial Cells / metabolism
  • Humans
  • Nitric Oxide Synthase Type III* / metabolism
  • Nitric Oxide* / metabolism
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt / metabolism


  • Nitric Oxide
  • Nitric Oxide Synthase Type III
  • Proto-Oncogene Proteins c-akt