Does autophagy play a key role in the protective effect of oleic acid against oxidative stress in endothelial cells?

Abstract

Endothelial dysfunction is a primary cause of cardiovascular complications that lead to atherosclerosis, while oxidative stress has been highligthted as one mechanism involved in endothelial dysfunction. Prevention of oxidative stress may then be a strategy to avoid endothelial dysfunction and cardiovascular disease. As the ability of oleic acid of reducing reactive oxygen species and related oxidative stress has been shown, other potential cellular mechanisms that could be responsible for the protective effect have to be evaluated. Autophagy is considered a cellular adaptive response under stressful conditions; thus, its role in the protective mechanism of oleic acid in stressed endothelial (EA.hy926) cells was assessed. To that end, cell viability and markers of oxidative status, such as reactive oxygen species, reduced glutathione, glutathione peroxidase, and reductase were evaluated. Moreover, the expression of several key autophagy-related proteins, such as microtubule-associated protein 1 light chain 3 beta and ubiquitin-binding protein p62/sequestosome 1, were investigated. The results showed that oleic acid within the micromolar range stimulated autophagy. However, when autophagy was inhibited in endothelial cells under oxidative stress, changes in the chemoprotective effect of oleic acid were minimal. These results suggest a limited contribution of autophagy to the protective effect of oleic acid under conditions of severe oxidative stress.