The pathophysiology underlying endothelial dysfunction is complex, but a higher abundance of reactive oxygen species (ROS) in the vasculature, stemming from ROS sources such as nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, xanthine oxidase, mitochondria, and uncoupled endothelial nitric oxide synthase (eNOS) [18, 29, 59], represents a key pathomechanism of all cardiovascular disease with associated endothelial dysfunction [36, 37]. The gene discussed is NOS3; the disease is endothelial dysfunction.