Lipid peroxidation and redox-sensitive signaling pathways.

A growing body of evidence suggests that many of the effects of vascular dysfunction on cardiovascular diseases are mediated by the products of nonenzymatic reactions, such as the peroxidative degradation of polyunsaturated fatty acids (ie, lipid peroxidation). These degradation products are electrophilic reactive compounds and are thought to have a major impact on human health and lifespan by acting on proteins and genes. The oxidized lipids bound to the biomacromolecules can be detected as constituents in human patients with increased risk factors or clinical manifestations of lifestyle-related diseases, such as atherosclerosis. However, it appears that there are several sensor mechanisms in which specific cellular proteins directly interact with these electrophilic molecules. Moreover, a number of lipid peroxidation products have been shown as inducers for activation of the redox-related cell signaling mechanism, which integrate with other signaling pathways to control cellular responses to extracellular stimuli.