Taking into consideration that BH4 is highly susceptible to oxidative degradation by •O2- or •ONOO-, the initial degradation of BH4 by ROS derived from another source induces eNOS uncoupling and the amplification of oxidative stress in conditions of hypercholesterolemia and atherosclerosis in human [82] and in apoE-/- mice [83]. This evidence concerns the gene NOS3 and Hypercholesterolemia.