The endothelial dysfunction of large vessels in hypercholesterolemia and other cardiovascular diseases has been attributed to the following: (a) a decrease in NO production or eNOS synthesis/activity; (b) excessive production of vascular ROS, where •O2- reacts with NO, resulting in the formation of •ONOO- and a decreased in the bioavailability of NO; (c) the local oxidation of circulating lipoproteins and/or (d) a decreased antioxidant capacity (see scheme in Figure 6). The gene discussed is NOS3; the disease is cardiovascular disorder.