title: Polyphenol fraction of extra virgin olive oil protects against endothelial dysfunction induced by high glucose and free fatty acids through modulation of nitric oxide and endothelin-1.
abstract: Epidemiological and clinical studies have reported that olive oil reduces the incidence of cardiovascular disease. However, the mechanisms involved in this beneficial effect have not been delineated. The endothelium plays an important role in blood pressure regulation through the release of potent vasodilator and vasoconstrictor agents such as nitric oxide (NO) and endothelin-1 (ET-1), respectively, events that are disrupted in type 2 diabetes. Extra virgin olive oil contains polyphenols, compounds that exert a biological action on endothelial function. This study analyzes the effects of olive oil polyphenols on endothelial dysfunction using an in vitro model that simulates the conditions of type 2 diabetes. Our findings show that high glucose and linoleic and oleic acids decrease endothelial NO synthase phosphorylation, and consequently intracellular NO levels, and increase ET-1 synthesis by ECV304 cells. These effects may be related to the stimulation of reactive oxygen species production in these experimental conditions. Hydroxytyrosol and the polyphenol extract from extra virgin olive oil partially reversed the above events. Moreover, we observed that high glucose and free fatty acids reduced NO and increased ET-1 levels induced by acetylcholine through the modulation of intracellular calcium concentrations and endothelial NO synthase phosphorylation, events also reverted by hydroxytyrosol and polyphenol extract. Thus, our results suggest a protective effect of olive oil polyphenols on endothelial dysfunction induced by hyperglycemia and free fatty acids.
authors.affiliation: Department of Physiology, Faculty of Pharmacy, University of Barcelona, Avda. Joan XXIII s/n, Barcelona E-08028, Spain.
authors.forename: Carolina Emilia
authors.initials: CE
authors.lastname: Storniolo
authors.affiliation: Department of Experimental Pathology, IIBB-CSIC, IDIBAPS, Barcelona E-08036, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Roselló-Catafau
authors.affiliation: Lipids and Vascular Risk Unit, Internal Medicine, University Hospital of Bellvitge, Hospitalet de Llobregat, Barcelona E-08907, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Pintó
authors.affiliation: Department of Physiology and Immunology, Faculty of Biology, University of Barcelona, Avda. Diagonal 485, Barcelona E-08028, Spain.
authors.forename: María Teresa
authors.initials: MT
authors.lastname: Mitjavila
authors.affiliation: Department of Physiology, Faculty of Pharmacy, University of Barcelona, Avda. Joan XXIII s/n, Barcelona E-08028, Spain. Electronic address: jjmoreno@ub.edu.
authors.forename: Juan José
authors.initials: JJ
authors.lastname: Moreno
mesh_terms: D002460:Cell Line; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000473:pathology; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D019332:Endothelin-1 / Q000096:biosynthesis*; D005230:Fatty Acids, Nonesterified / Q000009:adverse effects* / Q000494:pharmacology; D005947:Glucose / Q000009:adverse effects* / Q000494:pharmacology; D019787:Linoleic Acid / Q000009:adverse effects / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D019301:Oleic Acid / Q000009:adverse effects / Q000494:pharmacology; D000069463:Olive Oil / Q000737:chemistry*; D059808:Polyphenols / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D019332:Endothelin-1; D005230:Fatty Acids, Nonesterified; D000069463:Olive Oil; D059808:Polyphenols; D019301:Oleic Acid; D009569:Nitric Oxide; D019787:Linoleic Acid; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D005947:Glucose
keywords: Cell oxidative stress; ECV304 cells; Hyperglycemia; Linoleic acid; Oleic acid; Reactive oxygen species; Type 2 diabetes