It is well known that insufficient sleep is linked to increased cardiovascular risks due to the accumulation of oxidative stress, which contributes to endothelial inflammation and dysfunction. However, the underlying mechanism had not been elucidated until a recent trial conducted by Columbia University Irving Medical Center. Investigators recruited 35 healthy females who normally had adequate sleep to undergo a 6-week sleep-restricted experiment by reducing their sleep by 1.5 hours. It was found that mildly sleep-deprived females had elevated endothelial oxidative stress, which was consistent with previous studies. More importantly, the lack of endothelial antioxidant responses was noted despite the noticeable increase in endothelial oxidative stress. Reduced expression of DCUN1D3 regulator SRF was found to be fundamental to the lack of antioxidant response, which promoted proteasomal degradation. On the contrary, in adults with sufficient sleep, the expression of DCUN1D3 was not hindered, and the endothelial oxidative stress accumulated during the wakeful period can be cleared by an appropriate antioxidant response through the Nrf2 translocation pathway, thus preventing proteasomal degradation. One key question arising from this study is whether Nrf2 activators will have any possible therapeutic application, especially in areas of atherosclerosis and anti-inflammation, and further research is needed to answer this.

References

Shah R, Sci Rep. 2023;13(1):15360.