O2− can then react with NO to form peroxynitrite (ONOO−), a cytotoxic radical oxygen species that can oxidize BH4 and further promote the loss of this essential cofactor.196 The ratio of [NO]/[ONOO−] is a key indicator of eNOS coupling efficiency and directly related to the relative amounts of dimeric and monomeric eNOS present in the cell.197 Reversing endothelial dysfunction can therefore take many forms, including reducing oxidative stress, increasing NO bioavailability and eNOS coupling, and decreasing pro-inflammatory adhesion molecules and mediators. The gene discussed is NOS3; the disease is endothelial dysfunction.