Unveiling Protective Mechanisms of Wild Olive (Acebuche) Oil in Retinal Pigment Epithelial Cells with Hypertensive Phenotype

Abstract

Arterial hypertension leads to oxidative and inflammatory imbalances, triggering hyper-tensive organ damage through several pathways. We have previously described the antioxidant andanti-inflammatory properties of olive oil extracted from the wild olive tree (Olea europaea var.sylvestris, acebuche, ACE) against hypertensive ocular damage. The aim of this study was to clarifythe molecular mechanisms involved in the beneficial effect of ACE oil on hypertensive eyes, focusingon nitric oxide (NO)/arginine metabolism. To this end, we used retinal pigment epithelial cells(ARPE19) treated with angiotensin II as a hypertensive-like model. These cells were also incubatedwith extracellular vesicles (EVs) isolated from animals fed diets enriched in either ACE oil or extravirgin olive oil (EVOO), with the latter serving as a reference oil for comparison. Our results showedthat circulating ACE oil- and EVOO-derived EVs can modulate the production of reactive oxygenspecies by both NADPH oxidase and mitochondria, the activity and expression of l-arginine trans-porter CAT-1, angiotensin AT1 and AT2 receptors, and arginases, as well as the levels of NO andasymmetric dimethylarginine. Our findings demonstrate that: (1) changes in NO metabolism areinvolved in the protective effects of wild olive oil against hypertension-related ocular oxidative stress,and (2) these modifications appear to be mediated by EVs.