Figure 3.

Inhibitory signaling events against AngII/AT₁R-mediated senescence in VSMC. Various inhibitors that attenuate senescence via antagonizing oxidative stress have been reported. PGC-1α deficiency promotes vascular senescence with increased ROS and results in reduced expression of Sirt1 [76]. PGC-1α also maintains autophagy and a component of autophagy, autophagy related 5 (ATG5) to counter-regulate senescence [77]. Nrf2 plays a key role in protection of cellular senescence via PKA/CREB pathway [78]. Soluble Klotho, an antiaging hormone, attenuates AngII-induced VSMC senescence through Nrf2 induction and ROS attenuation [79]. Mitochondrial Sirt3 also protects against mtROS [76,80]. In addition, reduction in NAD⁺ exaggerates AngII-induced vascular senescence [76,81].