{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T02:59:47Z","timestamp":1781319587230,"version":"3.54.1"},"reference-count":59,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,2,24]],"date-time":"2025-02-24T00:00:00Z","timestamp":1740355200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,2,24]],"date-time":"2025-02-24T00:00:00Z","timestamp":1740355200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2026,6]]},"abstract":"\n Abstract<\/jats:title>\n \n Arterial hypertension leads to oxidative and inflammatory imbalances, triggering hypertensive organ damage through several pathways. We have previously described the antioxidant and anti\u2010inflammatory properties of olive oil extracted from the wild olive tree (\n Olea europaea<\/jats:italic>\n var.\n sylvestris<\/jats:italic>\n , acebuche, ACE) against hypertensive ocular damage. The aim of this study was to clarify the molecular mechanisms involved in the beneficial effect of ACE oil on hypertensive eyes, focusing on nitric oxide (NO)\/arginine metabolism. To this end, we used retinal pigment epithelial cells (ARPE19) treated with angiotensin II as a hypertensive\u2010like model. These cells were also incubated with extracellular vesicles (EVs) isolated from animals fed diets enriched in either ACE oil or extra virgin olive oil (EVOO), with the latter serving as a reference oil for comparison. Our results showed that circulating ACE oil\u2010 and EVOO\u2010derived EVs can modulate the production of reactive oxygen species by both NADPH oxidase and mitochondria, the activity and expression of\n l<\/jats:sc>\n \u2010arginine transporter CAT\u20101, angiotensin AT1 and AT2 receptors, and arginases, as well as the levels of NO and asymmetric dimethylarginine. Our findings demonstrate that: (1) changes in NO metabolism are involved in the protective effects of wild olive oil against hypertension\u2010related ocular oxidative stress, and (2) these modifications appear to be mediated by EVs.\n \n \n image<\/jats:alt-text>\n <\/jats:graphic>\n <\/jats:boxed-text>\n <\/jats:p>\n <\/jats:sec>\n \n Key points<\/jats:title>\n \n \n \n \n l<\/jats:sc>\n \u2010Arginine transport contributes to the beneficial effect of wild olive oil on the eyes of hypertensive mice.\n <\/jats:p>\n <\/jats:list-item>\n \n Extravesicular vesicles from wild olive oil (ACE\u2010EVs) prevent changes in nitric oxide (metabolism in hypertensive\u2010like retinal pigment epithelial cells.<\/jats:p>\n <\/jats:list-item>\n \n Reactive oxygen species produced by both NADPH oxidase and mitochondria can be mitigated by ACE\u2010EV treatment.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1113\/jp287367","type":"journal-article","created":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T18:45:34Z","timestamp":1741718734000},"page":"4166-4185","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Unveiling protective mechanisms of wild olive (acebuche) oil in retinal pigment epithelial cells with hypertensive phenotype"],"prefix":"10.1113","volume":"604","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9469-3850","authenticated-orcid":false,"given":"\u00c1lvaro","family":"Santana\u2010Garrido","sequence":"first","affiliation":[{"name":"Departamento de Fisiolog\u00eda, Facultad de Farmacia Universidad de Sevilla Sevilla Spain"},{"name":"Epidemiolog\u00eda Cl\u00ednica y Riesgo Cardiovascular, Instituto de Biomedicina de Sevilla (IBIS) Hospital Universitario Virgen del Roc\u00edo\/Consejo Superior de Investigaciones Cient\u00edficas\/Universidad de Sevilla Sevilla Spain"},{"name":"Department of Clinical Neuroscience St. Erik Eye Hospital, Karolinska Institutet Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1621-5335","authenticated-orcid":false,"given":"Claudia","family":"Reyes\u2010Goya","sequence":"additional","affiliation":[{"name":"Departamento de Fisiolog\u00eda, Facultad de Farmacia Universidad de Sevilla Sevilla Spain"},{"name":"Epidemiolog\u00eda Cl\u00ednica y Riesgo Cardiovascular, Instituto de Biomedicina de Sevilla (IBIS) Hospital Universitario Virgen del Roc\u00edo\/Consejo Superior de Investigaciones Cient\u00edficas\/Universidad de Sevilla Sevilla Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo","family":"Espinosa\u2010Mart\u00edn","sequence":"additional","affiliation":[{"name":"Departamento de Fisiolog\u00eda, Facultad de Farmacia Universidad de Sevilla Sevilla Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa M.","family":"Troya\u2010Toledo","sequence":"additional","affiliation":[{"name":"Departamento de Fisiolog\u00eda, Facultad de Farmacia Universidad de Sevilla Sevilla Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2926-2376","authenticated-orcid":false,"given":"Helder","family":"Andr\u00e9","sequence":"additional","affiliation":[{"name":"Department of Clinical Neuroscience St. Erik Eye Hospital, Karolinska Institutet Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2719-8825","authenticated-orcid":false,"given":"Alfonso","family":"Mate","sequence":"additional","affiliation":[{"name":"Departamento de Fisiolog\u00eda, Facultad de Farmacia Universidad de Sevilla Sevilla Spain"},{"name":"Epidemiolog\u00eda Cl\u00ednica y Riesgo Cardiovascular, Instituto de Biomedicina de Sevilla (IBIS) Hospital Universitario Virgen del Roc\u00edo\/Consejo Superior de Investigaciones Cient\u00edficas\/Universidad de Sevilla Sevilla Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2999-3582","authenticated-orcid":false,"given":"Carmen M.","family":"V\u00e1zquez","sequence":"additional","affiliation":[{"name":"Departamento de Fisiolog\u00eda, Facultad de Farmacia Universidad de Sevilla Sevilla Spain"},{"name":"Epidemiolog\u00eda Cl\u00ednica y Riesgo Cardiovascular, Instituto de Biomedicina de Sevilla (IBIS) Hospital Universitario Virgen del Roc\u00edo\/Consejo Superior de Investigaciones Cient\u00edficas\/Universidad de Sevilla Sevilla Spain"},{"name":"Department of Clinical Neuroscience St. Erik Eye Hospital, Karolinska Institutet Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,2,24]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.steroids.2020.108701"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.foodchem.2017.02.011"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1080\/23723556.2022.2044263"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1080\/20013078.2019.1626654"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.R084640"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(76)90527-3"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.110.222703"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-022-00763-8"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joim.2021.09.006"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2009.09.004"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells10071763"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00138.2012"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu14112200"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2020.566410"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tjo.2011.11.001"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox10020238"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1039\/D2FO00876A"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-021-00265-2"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2010.03.003"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/ceo.12905"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13544"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.117.07802"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00726-019-02788-1"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1089\/jop.2011.0155"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2020.101799"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11906-012-0283-6"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.21037\/atm-22-5634"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYP.0000000000000090"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu16030409"},{"key":"e_1_2_5_31_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201601244RR"},{"key":"e_1_2_5_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00394-021-02594-0"},{"key":"e_1_2_5_33_1","doi-asserted-by":"publisher","DOI":"10.1080\/02713683.2017.1319491"},{"key":"e_1_2_5_34_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.117.09321"},{"key":"e_1_2_5_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-020-01483-2"},{"key":"e_1_2_5_36_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2013.00173"},{"key":"e_1_2_5_37_1","doi-asserted-by":"publisher","DOI":"10.2174\/1381612826666200115092015"},{"key":"e_1_2_5_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2021.108518"},{"key":"e_1_2_5_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep14362"},{"key":"e_1_2_5_40_1","doi-asserted-by":"publisher","DOI":"10.1042\/CS20160092"},{"key":"e_1_2_5_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2021.108892"},{"key":"e_1_2_5_42_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.0022-3042.2001.00723.x"},{"key":"e_1_2_5_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-008-9641-9"},{"key":"e_1_2_5_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2014.12.007"},{"key":"e_1_2_5_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2020.165993"},{"key":"e_1_2_5_46_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.18-24803"},{"key":"e_1_2_5_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/mnfr.202200623"},{"key":"e_1_2_5_48_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13105-022-00916-2"},{"key":"e_1_2_5_49_1","first-page":"161","article-title":"NADPH oxidase\u2010induced oxidative stress in the eyes of hypertensive rats","volume":"27","author":"Santana\u2010Garrido \u00c1.","year":"2021","journal-title":"Molecular Vision"},{"key":"e_1_2_5_50_1","doi-asserted-by":"publisher","DOI":"10.3390\/foods10091993"},{"key":"e_1_2_5_51_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox9090885"},{"key":"e_1_2_5_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2016.295"},{"key":"e_1_2_5_53_1","first-page":"1","article-title":"The mechanisms of natural products for eye disorders by targeting mitochondrial dysfunction","volume":"15","author":"Sun G.\u2010F.","year":"2024","journal-title":"Frontiers in Pharmacology"},{"key":"e_1_2_5_54_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11906-018-0823-9"},{"key":"e_1_2_5_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2020.100919"},{"key":"e_1_2_5_56_1","doi-asserted-by":"publisher","DOI":"10.1002\/tox.24416"},{"key":"e_1_2_5_57_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40135-017-0153-0"},{"key":"e_1_2_5_58_1","doi-asserted-by":"publisher","DOI":"10.1515\/cclm-2016-0036"},{"issue":"3","key":"e_1_2_5_59_1","first-page":"2","article-title":"Association between postillumination pupil response and glaucoma severity: A cross\u2010sectional analysis of the LIGHT study","volume":"63","author":"Yoshikawa T.","year":"2022","journal-title":"Investigative Opthalmology & Visual Science"},{"key":"e_1_2_5_60_1","doi-asserted-by":"publisher","DOI":"10.1002\/jev2.12358"}],"container-title":["The Journal of Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/JP287367","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/full-xml\/10.1113\/JP287367","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/JP287367","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T02:33:57Z","timestamp":1781318037000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.1113\/JP287367"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,24]]},"references-count":59,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2026,6]]}},"alternative-id":["10.1113\/JP287367"],"URL":"https:\/\/doi.org\/10.1113\/jp287367","archive":["Portico"],"relation":{},"ISSN":["0022-3751","1469-7793"],"issn-type":[{"value":"0022-3751","type":"print"},{"value":"1469-7793","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,24]]},"assertion":[{"value":"2024-07-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-07","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-24","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}