Effet protecteur des acides gras contre le stress oxydatif : Implication en physiopathologie vasculaire

Inserm U466 et laboratoire de biochimie, IFR31, CHU Rangueil, 31432, Toulouse, France

Reçu : 20 Septembre 2005
Accepté : 9 Novembre 2005

Abstract

Oxidative stress play a major role in the genesis and the evolution of vascular pathologies. Recent data suggest that redox mechanisms are involved in the signaling network of vascular cells and the physiology of the vascular wall. Experimental cell models allow to analyse the biological effect of pro-oxidants, and the regulation exerted by antioxidants and cytoprotective agents.

Fatty acids play a complex role in atherosclerosis, since they exhibit both anti and proatherogenic properties, as function of their concentration and insaturation level. Beside their role in cell metabolism and mitochondrial b-oxidation, fatty acids activate various signaling pathways, and could modulate intracellular oxidative stress via an uncoupling effect on mitochondria. We report here that fatty acids protect against mitochondrial oxidative stress by activating cellular glutathione peroxidase (GPX) activity. This effect is independent of the chain length and unsaturation level. EGF receptor is activated by fatty acids and involved in their protective effect against mitochondrial oxidative stress and GPX activation, and similar protective results are observed with EGF. Oleic acid and EGF protect DNA against the formation of 8oxodG lesions occurring subsequently to oxidative stress. Taken together, this new ‘antioxidant’ and cytoprotective property of fatty acids and EGF could participate to the stabilization of atherosclerotic plaque, and the more general anti-atherogenic properties of oleic acid.