Cardiovascular Division (Clinical)

Despite the fundamental biological role of oxygen as an efficient producer of energy, an altered form of oxygen – with modifications in key chemical bonds that may potentially result in alterations in cellular structure and function – contributes to disease progression. Reactive oxygen species (ROS) include both free radicals (that typically have an oxygen- or nitrogen-based unpaired elec-tron in their outer orbitals) and other species (eg, hydrogen peroxide) that act as oxidants. The mitochondria and cellular membrane oxidases (eg, NADPH oxidase) are major sources of ROS (Table 1). The byproducts associated with metabolism of arachidonic acid by cyclooxygenase, lipoxygenase, and cytochrome p-450 mono-oxygenase also result in the production of ROS. The targets for damage by ROS are not only lipids, (eg, polyunsaturated fatty acids in cellular mem-branes and low density lipoproteins [LDL]), but also proteins and nucleic acids. Lipid peroxidation products react strongly with various biological substrates leading to cellular injury. Oxidative damage to the polyunsaturated fatty acids of membrane phospholipids leads to destabilization in their intermolecular packing characteristics and subsequent loss of membrane integrity. Lipid per-oxides break down into smaller molecules that remain either covalently linked to the phospholipid glycerol backbone or are released into the cytosol. In addition, the oxidized LDL particle does no