Hyperlipidemia can reduce NO production and exacerbate endothelial damage by downregulating eNOS through signaling pathways, such as HMGB1/TLR4/Caveolin-1 (Gliozzi et al., 2019), NRF2 (Abu-Saleh et al., 2021), and AMPK/PI3K/AkteNOS (García-Prieto et al., 2015). The gene discussed is NOS3; the disease is hyperlipidemia.