Cellular senescence mediates doxorubicin chemotherapy-induced vascular endothelial dysfunction: translational evidence of prevention with senolytic treatment

We demonstrate that cellular senescence contributes to doxorubicin-related vascular endothelial dysfunction and establishes efficacy for the use of senolytic therapy to improve vascular function following doxorubicin administration. Mechanistically, we found that cellular senescence reduced NO bioavailability and promoted excessive production of vascular mitochondrial superoxide-related oxidative stress, both of which were prevented with senolytic therapy. We translated these findings to humans and showed that ex vivo exposure to doxorubicin impaired arteriole endothelial function, which was prevented with senolytic exposure.