Nitric oxide, peroxynitrite and lipoxygenase in atherogenesis: mechanistic insights

Nitric oxide (NO) is a free radical species that diffuses and concentrates in the hydrophobic core of low-density lipoprotein (LDL) to serve as a potent antioxidant. Peroxynitrite, the product of the diffusion-limited reaction between NO and superoxide anion, as well as lipoxygenase, represent relevant mediators of oxidative modifications in LDL. The focus of this review is the analysis of interactions between NO, peroxynitrite and lipoxygenase during LDL oxidation, which are relevant in the development of the early steps as well as progression of atherosclerosis. The role of CO2 to redirect peroxynitrite reactivity in LDL, as well as the lipophilic antioxidant sparing actions of NO, ascorbate and CO2 is also analyzed. In this context, the effects of novel potential pharmacological strategies against atherosclerosis such as Mn(III)porphyrins will be discussed.