Le stress oxydant, composante physiopathologique de l'athérosclérose

Reactive oxygen and nitrogen species (ROS-RNS) are constitutionally generated by the various cells of the arterial wall. Several intracellular enzymes are implicated in this ROS/RNS formation: NAD(P)H oxidases, NO synthases, mitochondrial respiratory chain pathway… Both enzymatic and nonenzymatic antioxidants allow the degradation of the ROS/RNS, thus maintaining a physiological equilibrium between pro-oxidants and antioxidants. In pathophysiological circumstances, a alteration of redox status occurs, that generates vascular cell dysfunction. Risk factors for the atherosclerotic process such as hypertension, hypercholesterolemia, diabetes…generate an excess of ROS production by stimulation of either NAD(P)H oxidases or the mitochondrial respiratory chain, or both. Overproduction of superoxide anion results in its combination with nitric oxide to form peroxinitrite, thereby decreasing the biodisponibility of nitric oxide. Such pro-oxidant conditions favour LDL oxidation, the release of pro-inflammatory biofactors and/or growth factors. They also provoke both the apoptotic process and necrosis, that are important features responsible for atherosclerotic lesion progression and rupture, leading to the clinical events of atherosclerosis.