NO bioavailability and disrupted NO-sGC-cGMP signaling may be impaired by several mechanisms, including endothelial dysfunction and concomitant reduction in endothelial nitric oxide synthase (eNOS) activity, increased levels of the nitric oxide synthesis (NOS) inhibitor asymmetric dimethyl arginine, and increased oxidative stress and reactive oxygen species that react with NO (Lourenço et al., 2017). The gene discussed is NOS3; the disease is endothelial dysfunction.