{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T09:46:13Z","timestamp":1791539173320,"version":"4.3.4"},"reference-count":187,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,2,16]],"date-time":"2023-02-16T00:00:00Z","timestamp":1676505600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003093","name":"Fundamental Research Grant Scheme (FRGS)","doi-asserted-by":"publisher","award":["FRGS\/1\/2019\/SKK08\/UKM\/03\/3"],"award-info":[{"award-number":["FRGS\/1\/2019\/SKK08\/UKM\/03\/3"]}],"id":[{"id":"10.13039\/501100003093","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003093","name":"Fundamental Research Grant Scheme (FRGS)","doi-asserted-by":"publisher","award":["FF-2020-295"],"award-info":[{"award-number":["FF-2020-295"]}],"id":[{"id":"10.13039\/501100003093","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ministry of Education Malaysia and Faculty of Medicine, National University of Malaysia (UKM)","award":["FRGS\/1\/2019\/SKK08\/UKM\/03\/3"],"award-info":[{"award-number":["FRGS\/1\/2019\/SKK08\/UKM\/03\/3"]}]},{"name":"Ministry of Education Malaysia and Faculty of Medicine, National University of Malaysia (UKM)","award":["FF-2020-295"],"award-info":[{"award-number":["FF-2020-295"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Pharmacologists have been emphasizing and applying plant and herbal-based treatments in vascular diseases for decades now. Olives, for example, are a traditional symbol of the Mediterranean diet. Hydroxytyrosol is an olive-derived compound known for its antioxidant and cardioprotective effects. Acknowledging the merit of antioxidants in maintaining endothelial function warrants the application of hydroxytyrosol in endothelial dysfunction salvage and recovery. Endothelial dysfunction (ED) is an impairment of endothelial cells that adversely affects vascular homeostasis. Disturbance in endothelial functioning is a known precursor for atherosclerosis and, subsequently, coronary and peripheral artery disease. However, the effects of hydroxytyrosol on endothelial functioning were not extensively studied, limiting its value either as a nutraceutical supplement or in clinical trials. The action of hydroxytyrosol in endothelial functioning at a cellular and molecular level is gathered and summarized in this review. The favorable effects of hydroxytyrosol in the improvement of endothelial functioning from in vitro and in vivo studies were scrutinized. We conclude that hydroxytyrosol is capable to counteract oxidative stress, inflammation, vascular aging, and arterial stiffness; thus, it is beneficial to preserve endothelial function both in vitro and in vivo. Although not specifically for endothelial dysfunction, hydroxytyrosol safety and efficacy had been demonstrated via in vivo and clinical trials for cardiovascular-related studies.<\/jats:p>","DOI":"10.3390\/molecules28041861","type":"journal-article","created":{"date-parts":[[2023,2,16]],"date-time":"2023-02-16T02:04:03Z","timestamp":1676513043000},"page":"1861","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Effects of Hydroxytyrosol in Endothelial Functioning: A Comprehensive Review"],"prefix":"10.3390","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5394-7068","authenticated-orcid":false,"given":"Ubashini","family":"Vijakumaran","sequence":"first","affiliation":[{"name":"Centre for Tissue Engineering & Regenerative Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Cheras, Kuala Lumpur 56000, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janushaa","family":"Shanmugam","sequence":"additional","affiliation":[{"name":"Centre for Tissue Engineering & Regenerative Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Cheras, Kuala Lumpur 56000, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun Wei","family":"Heng","sequence":"additional","affiliation":[{"name":"Centre for Tissue Engineering & Regenerative Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Cheras, Kuala Lumpur 56000, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siti Sarah","family":"Azman","sequence":"additional","affiliation":[{"name":"Centre for Tissue Engineering & Regenerative Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Cheras, Kuala Lumpur 56000, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6162-4405","authenticated-orcid":false,"given":"Muhammad Dain","family":"Yazid","sequence":"additional","affiliation":[{"name":"Centre for Tissue Engineering & Regenerative Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Cheras, Kuala Lumpur 56000, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nur Atiqah","family":"Haizum Abdullah","sequence":"additional","affiliation":[{"name":"Centre for Tissue Engineering & Regenerative Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Cheras, Kuala Lumpur 56000, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3965-1850","authenticated-orcid":false,"given":"Nadiah","family":"Sulaiman","sequence":"additional","affiliation":[{"name":"Centre for Tissue Engineering & Regenerative Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Cheras, Kuala Lumpur 56000, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Kr\u00fcger-Genge, A., Blocki, A., Franke, R.P., and Jung, F. (2019). Vascular Endothelial Cell Biology: An Update. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20184411"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1412","DOI":"10.1016\/j.cca.2010.06.019","article-title":"Mechanism of endothelial dysfunction in chronic kidney disease","volume":"411","author":"Malyszko","year":"2010","journal-title":"Clin. Chim. Acta"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1097\/FJC.0000000000001087","article-title":"Endothelium-Dependent Hyperpolarization: The Evolution of Myoendothelial Microdomains","volume":"78","author":"Garland","year":"2021","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1007\/s00441-021-03471-2","article-title":"Endothelial cells and coagulation","volume":"387","author":"Neubauer","year":"2022","journal-title":"Cell Tissue Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2216","DOI":"10.1016\/j.bbadis.2013.08.006","article-title":"Endothelial dysfunction\u2014A major mediator of diabetic vascular disease","volume":"1832","author":"Sena","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"109485","DOI":"10.1016\/j.cellsig.2019.109485","article-title":"Endothelial tight junctions and their regulatory signaling pathways in vascular homeostasis and disease","volume":"66","author":"Cong","year":"2020","journal-title":"Cell. Signal."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Yau, J.W., Teoh, H., and Verma, S. (2015). Endothelial cell control of thrombosis. BMC Cardiovasc. Disord., 15.","DOI":"10.1186\/s12872-015-0124-z"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"444","DOI":"10.5455\/medarh.2018.72.444-448","article-title":"Tissue Augmentation in Wound Healing: The Role of Endothelial and Epithelial Cells","volume":"72","author":"Velnar","year":"2018","journal-title":"Med. Arch."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e108","DOI":"10.1161\/ATVBAHA.117.309813","article-title":"Endothelial Functions","volume":"37","author":"Godo","year":"2017","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1328","DOI":"10.1136\/bmj.316.7141.1328","article-title":"Endothelial cell activation. A central pathophysiological process","volume":"316","author":"Hunt","year":"1998","journal-title":"BMJ"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1093\/cvr\/cvaa085","article-title":"Endothelial function in cardiovascular medicine: A consensus paper of the European Society of Cardiology Working Groups on Atherosclerosis and Vascular Biology, Aorta and Peripheral Vascular Diseases, Coronary Pathophysiology and Microcirculation, and Thrombosis","volume":"117","author":"Alexander","year":"2020","journal-title":"Cardiovasc. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"978378","DOI":"10.3389\/fphys.2022.978378","article-title":"Endothelial dysfunction due to the inhibition of the synthesis of nitric oxide: Proposal and characterization of an in vitro cellular model","volume":"13","author":"Cordeiro","year":"2022","journal-title":"Front. Physiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.taap.2017.11.004","article-title":"H2S protects lipopolysaccharide-induced inflammation by blocking NF\u03baB transactivation in endothelial cells","volume":"338","author":"Bourque","year":"2018","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_14","first-page":"291","article-title":"Endothelial dysfunction and cardiovascular disease","volume":"2014","author":"Widmer","year":"2014","journal-title":"Glob. Cardiol. Sci. Pr."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"787541","DOI":"10.3389\/fphar.2021.787541","article-title":"Dysfunctional Vascular Endothelium as a Driver of Atherosclerosis: Emerging Insights Into Pathogenesis and Treatment","volume":"12","author":"Botts","year":"2021","journal-title":"Front. Pharm."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e26","DOI":"10.1161\/ATVBAHA.116.306940","article-title":"Endothelium","volume":"36","author":"Boulanger","year":"2016","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1186\/s12944-017-0625-0","article-title":"Hypertriglyceridemia and atherosclerosis","volume":"16","author":"Peng","year":"2017","journal-title":"Lipids Health Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1038\/s41375-021-01383-2","article-title":"Endothelial dysfunction and thromboembolism in children, adolescents, and young adults with acute lymphoblastic leukemia","volume":"36","author":"Grell","year":"2022","journal-title":"Leukemia"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1016\/j.avsg.2017.06.131","article-title":"The Role of Endothelial Dysfunction and Inflammation in Chronic Venous Disease","volume":"46","author":"Cardoso","year":"2018","journal-title":"Ann. Vasc. Surg."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1007\/5584_2016_90","article-title":"Endothelial Dysfunction and Hypertension","volume":"956","author":"Konukoglu","year":"2017","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"798958","DOI":"10.3389\/fmed.2021.798958","article-title":"Endothelial Dysfunction in Hypertension: Current Concepts and Clinical Implications","volume":"8","author":"Gallo","year":"2022","journal-title":"Front. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1249\/JES.0000000000000065","article-title":"The Vascular Endothelium in Chronic Kidney Disease: A Novel Target for Aerobic Exercise","volume":"44","author":"Martens","year":"2016","journal-title":"Exerc. Sport Sci. Rev."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1177\/2047487319884246","article-title":"Assessment of peripheral endothelial function predicts future risk of solid-tumor cancer","volume":"27","author":"Toya","year":"2020","journal-title":"Eur. J. Prev. Cardiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.amjms.2021.12.010","article-title":"Endothelial Dysfunction in COVID-19 Infection","volume":"363","author":"Otifi","year":"2022","journal-title":"Am. J. Med. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"643810","DOI":"10.3389\/fcell.2021.643810","article-title":"Chronic Inhibition of mROS Protects Against Coronary Endothelial Dysfunction in Mice With Diabetes","volume":"9","author":"Xing","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/s12970-019-0269-8","article-title":"Effects of ascorbic acid supplementation on oxidative stress markers in healthy women following a single bout of exercise","volume":"16","author":"Yimcharoen","year":"2019","journal-title":"J. Int. Soc. Sports Nutr."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"11410","DOI":"10.1039\/D2FO01945K","article-title":"Biological effects of the olive tree and its derivatives on the skin","volume":"13","year":"2022","journal-title":"Food Funct."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Mart\u00ednez-Zamora, L., Pe\u00f1alver, R., Ros, G., and Nieto, G. (2021). Olive Tree Derivatives and Hydroxytyrosol: Their Potential Effects on Human Health and Its Use as Functional Ingredient in Meat. Foods, 10.","DOI":"10.3390\/foods10112611"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1016\/j.neurol.2019.07.017","article-title":"Extra-virgin olive oil for potential prevention of Alzheimer disease","volume":"175","author":"Jackson","year":"2019","journal-title":"Rev. Neurol. (Paris)"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"682","DOI":"10.3390\/antiox4040682","article-title":"Olive Tree (Olea europeae L.) Leaves: Importance and Advances in the Analysis of Phenolic Compounds","volume":"4","author":"Abaza","year":"2015","journal-title":"Antioxidants"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1315202","DOI":"10.1155\/2020\/1315202","article-title":"Comparative Study on Beneficial Effects of Hydroxytyrosol- and Oleuropein-Rich Olive Leaf Extracts on High-Fat Diet-Induced Lipid Metabolism Disturbance and Liver Injury in Rats","volume":"2020","author":"Fki","year":"2020","journal-title":"Biomed. Res. Int."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Gorzynik-Debicka, M., Przychodzen, P., Cappello, F., Kuban-Jankowska, A., Marino Gammazza, A., Knap, N., Wozniak, M., and Gorska-Ponikowska, M. (2018). Potential Health Benefits of Olive Oil and Plant Polyphenols. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19030686"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1111\/j.1753-4887.2009.00248.x","article-title":"Olive tree (Olea europaea) leaves: Potential beneficial effects on human health","volume":"67","author":"El","year":"2009","journal-title":"Nutr. Rev."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Borjan, D., Leitgeb, M., Knez, \u017d., and Hrn\u010di\u010d, M.K. (2020). Microbiological and Antioxidant Activity of Phenolic Compounds in Olive Leaf Extract. Molecules, 25.","DOI":"10.3390\/molecules25245946"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Bucciantini, M., Leri, M., Nardiello, P., Casamenti, F., and Stefani, M. (2021). Olive Polyphenols: Antioxidant and Anti-Inflammatory Properties. Antioxidants, 10.","DOI":"10.3390\/antiox10071044"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"879118","DOI":"10.3389\/fphar.2022.879118","article-title":"Olive Leaves as a Potential Phytotherapy in the Treatment of COVID-19 Disease; A Mini-Review","volume":"13","author":"Abdelgawad","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1089\/jmf.2019.0136","article-title":"Antiproliferative Activity of Olive Extract Rich in Polyphenols and Modified Pectin on Bladder Cancer Cells","volume":"23","year":"2020","journal-title":"J. Med. Food"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Pang, K.L., Lumintang, J.N., and Chin, K.Y. (2021). Thyroid-Modulating Activities of Olive and Its Polyphenols: A Systematic Review. Nutrients, 13.","DOI":"10.3390\/nu13020529"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2111","DOI":"10.1007\/s00394-020-02397-9","article-title":"The effect of olive leaf extract on cardiovascular health markers: A randomized placebo-controlled clinical trial","volume":"60","author":"Stevens","year":"2021","journal-title":"Eur. J. Nutr."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e57","DOI":"10.1017\/jns.2020.50","article-title":"Table olives and health: A review","volume":"9","author":"Rocha","year":"2020","journal-title":"J. Nutr. Sci."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"L\u00f3pez-L\u00f3pez, A., Cort\u00e9s-Delgado, A., and Garrido-Fern\u00e1ndez, A. (2020). Impact of Processing and Extraction on the Minor Components of Green Spanish-Style Gordal Table Olive Fat, as Assessed by Innovative Approaches. Foods, 9.","DOI":"10.3390\/foods9121907"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"460434","DOI":"10.1016\/j.chroma.2019.460434","article-title":"Table olive polyphenols: A simultaneous determination by liquid chromatography-mass spectrometry","volume":"1609","author":"Juan","year":"2020","journal-title":"J. Chromatogr. A"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.maturitas.2018.10.013","article-title":"Olive oil consumption and human health: A narrative review","volume":"118","author":"Foscolou","year":"2018","journal-title":"Maturitas"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Mazzocchi, A., Leone, L., Agostoni, C., and Pali-Sch\u00f6ll, I. (2019). The Secrets of the Mediterranean Diet. Does [Only] Olive Oil Matter?. Nutrients, 11.","DOI":"10.3390\/nu11122941"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Boskou, D. (2008). Olive Oil: Minor Constituents and Health, CRC Press.","DOI":"10.1201\/9781420059946"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Pedan, V., Popp, M., Rohn, S., Nyfeler, M., and Bongartz, A. (2019). Characterization of Phenolic Compounds and Their Contribution to Sensory Properties of Olive Oil. Molecules, 24.","DOI":"10.3390\/molecules24112041"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1016\/S0955-2863(02)00229-2","article-title":"Major phenolic compounds in olive oil: Metabolism and health effects","volume":"13","author":"Tuck","year":"2002","journal-title":"J. Nutr. Biochem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.tifs.2018.05.001","article-title":"Olive oil and its principal bioactive compound: Hydroxytyrosol\u2014A review of the recent literature","volume":"77","author":"Wani","year":"2018","journal-title":"Trends Food Sci. Technol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.jbiotec.2019.12.016","article-title":"Hydroxytyrosol: A natural compound with promising pharmacological activities","volume":"309","author":"Bertelli","year":"2020","journal-title":"J. Biotechnol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1007\/s11130-012-0315-z","article-title":"Comprehensive analysis of polyphenols in 55 extra virgin olive oils by HPLC-ECD and their correlation with antioxidant activities","volume":"67","author":"Bayram","year":"2012","journal-title":"Plant Foods Hum. Nutr."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1021\/jf030525l","article-title":"Effect of cultivar and processing method on the contents of polyphenols in table olives","volume":"52","author":"Romero","year":"2004","journal-title":"J. Agric. Food Chem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/S0014-5793(00)01216-3","article-title":"Olive oil phenolics are dose-dependently absorbed in humans","volume":"468","author":"Visioli","year":"2000","journal-title":"FEBS Lett."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1016\/j.fct.2013.01.030","article-title":"Toxicological evaluation of pure hydroxytyrosol","volume":"55","author":"Canut","year":"2013","journal-title":"Food Chem. Toxicol."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Nikou, T., Sakavitsi, M.E., Kalampokis, E., and Halabalaki, M. (2022). Metabolism and Bioavailability of Olive Bioactive Constituents Based on In Vitro, In Vivo and Human Studies. Nutrients, 14.","DOI":"10.3390\/nu14183773"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Bender, C., Strassmann, S., and Golz, C. (2022). Oral bioavailability and metabolism of hydroxytyrosol from food supplements. Nutrients, 15.","DOI":"10.1101\/2022.11.16.516752"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"9104208","DOI":"10.1155\/2016\/9104208","article-title":"Absorption, Metabolism, and Excretion by Freely Moving Rats of 3,4-DHPEA-EDA and Related Polyphenols from Olive Fruits (Olea europaea)","volume":"2016","author":"Kano","year":"2016","journal-title":"J. Nutr. Metab."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1002\/bmc.3389","article-title":"Fast determination of virgin olive oil phenolic metabolites in human high-density lipoproteins","volume":"29","author":"Montes","year":"2015","journal-title":"Biomed. Chromatogr."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA), Turck, D., Bresson, J.-L., Burlingame, B., Dean, T., Fairweather-Tait, S., Heinonen, M., Hirsch-Ernst, K.I., Mangelsdorf, I., and McArdle, H.J. (2017). Safety of hydroxytyrosol as a novel food pursuant to Regulation (EC) No 258\/97. EFSA J., 15, e04728.","DOI":"10.2903\/j.efsa.2017.4728"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"e34","DOI":"10.1056\/NEJMoa1800389","article-title":"Primary Prevention of Cardiovascular Disease with a Mediterranean Diet Supplemented with Extra-Virgin Olive Oil or Nuts","volume":"378","author":"Estruch","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1161\/CIRCRESAHA.118.313348","article-title":"The Mediterranean Diet and Cardiovascular Health","volume":"124","author":"Gea","year":"2019","journal-title":"Circ. Res."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Mart\u00ednez, L., Ros, G., and Nieto, G. (2018). Hydroxytyrosol: Health Benefits and Use as Functional Ingredient in Meat. Med., 5.","DOI":"10.3390\/medicines5010013"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"656272","DOI":"10.3389\/fphar.2021.656272","article-title":"Hydroxytyrosol Acetate Inhibits Vascular Endothelial Cell Pyroptosis via the HDAC11 Signaling Pathway in Atherosclerosis","volume":"12","author":"Yao","year":"2021","journal-title":"Front. Pharm."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Nani, A., Murtaza, B., Sayed Khan, A., Khan, N.A., and Hichami, A. (2021). Antioxidant and Anti-Inflammatory Potential of Polyphenols Contained in Mediterranean Diet in Obesity: Molecular Mechanisms. Molecules, 26.","DOI":"10.3390\/molecules26040985"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2241","DOI":"10.1021\/acs.jafc.1c07568","article-title":"Hydroxytyrosol Alleviates Dextran Sulfate Sodium-Induced Colitis by Modulating Inflammatory Responses, Intestinal Barrier, and Microbiome","volume":"70","author":"Wang","year":"2022","journal-title":"J. Agric. Food Chem."},{"key":"ref_65","first-page":"591","article-title":"Antiplatelet effect of new lipophilic hydroxytyrosol alkyl ether derivatives in human blood","volume":"52","author":"Guerrero","year":"2012","journal-title":"Eur. J. Nutr."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"D\u2019Angelo, C., Franceschelli, S., Quiles, J.L., and Speranza, L. (2020). Wide Biological Role of Hydroxytyrosol: Possible Therapeutic and Preventive Properties in Cardiovascular Diseases. Cells, 9.","DOI":"10.3390\/cells9091932"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Gallardo-Fern\u00e1ndez, M., Hornedo-Ortega, R., Alonso-Bellido, I.M., Rodr\u00edguez-G\u00f3mez, J.A., Troncoso, A.M., Garc\u00eda-Parrilla, M.C., Venero, J.L., Espinosa-Oliva, A.M., and Pablos, R.M. (2019). Hydroxytyrosol Decreases LPS- and \u03b1-Synuclein-Induced Microglial Activation In Vitro. Antioxidants, 9.","DOI":"10.3390\/antiox9010036"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Kamil, K., Yazid, M.D., Idrus, R.B.H., and Kumar, J. (2020). Hydroxytyrosol Promotes Proliferation of Human Schwann Cells: An In Vitro Study. Int. J. Environ. Res. Public Health, 17.","DOI":"10.3390\/ijerph17124404"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"741444","DOI":"10.3389\/fchem.2021.741444","article-title":"Novel Hydroxytyrosol-Donepezil Hybrids as Potential Antioxidant and Neuroprotective Agents","volume":"9","author":"Costanzo","year":"2021","journal-title":"Front. Chem."},{"key":"ref_70","first-page":"18","article-title":"Hydroxytyrosol and potential uses in cardiovascular diseases, cancer, and AIDS","volume":"1","year":"2014","journal-title":"Front. Nutr."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Carluccio, M.A., Martinelli, R., Massaro, M., Calabriso, N., Scoditti, E., Maffia, M., Verri, T., Gatta, V., and De Caterina, R. (2021). Nutrigenomic Effect of Hydroxytyrosol in Vascular Endothelial Cells: A Transcriptomic Profile Analysis. Nutrients, 13.","DOI":"10.3390\/nu13113990"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"7651","DOI":"10.3390\/nu7095356","article-title":"Effects of Olive Oil on Markers of Inflammation and Endothelial Function-A Systematic Review and Meta-Analysis","volume":"7","author":"Schwingshackl","year":"2015","journal-title":"Nutrients"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/j.ccc.2019.12.009","article-title":"Nitric Oxide and Endothelial Dysfunction","volume":"36","author":"Cyr","year":"2020","journal-title":"Crit. Care Clin."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"4","DOI":"10.2174\/157016112798829760","article-title":"The role of nitric oxide on endothelial function","volume":"10","author":"Tousoulis","year":"2012","journal-title":"Curr. Vasc. Pharm."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"06e403","DOI":"10.1116\/1.5042752","article-title":"Nitric oxide-mediated fibrinogen deposition prevents platelet adhesion and activation","volume":"13","author":"Zang","year":"2018","journal-title":"Biointerphases"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"5764","DOI":"10.2174\/0929867326666181213093152","article-title":"Nitric Oxide in Life and Death of Neutrophils","volume":"26","author":"Galkina","year":"2019","journal-title":"Curr. Med. Chem."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1222","DOI":"10.1253\/circj.CJ-17-0034","article-title":"Enhancement of Nitric Oxide Production Is Responsible for Minimal Intimal Hyperplasia of Autogenous Rabbit Arterial Grafts","volume":"81","author":"Tabata","year":"2017","journal-title":"Circ. J."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"121254","DOI":"10.1016\/j.biomaterials.2021.121254","article-title":"Nitric oxide releasing nanomatrix gel treatment inhibits venous intimal hyperplasia and improves vascular remodeling in a rodent arteriovenous fistula","volume":"280","author":"Somarathna","year":"2022","journal-title":"Biomaterials"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.vph.2017.05.005","article-title":"Oxidative stress and reactive oxygen species in endothelial dysfunction associated with cardiovascular and metabolic diseases","volume":"100","author":"Incalza","year":"2018","journal-title":"Vasc. Pharm."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.tplants.2016.08.002","article-title":"ROS Are Good","volume":"22","author":"Mittler","year":"2017","journal-title":"Trends Plant Sci."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1039241","DOI":"10.3389\/fimmu.2022.1039241","article-title":"ROS-triggered endothelial cell death mechanisms: Focus on pyroptosis, parthanatos, and ferroptosis","volume":"13","author":"Zheng","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Senoner, T., and Dichtl, W. (2019). Oxidative Stress in Cardiovascular Diseases: Still a Therapeutic Target?. Nutrients, 11.","DOI":"10.3390\/nu11092090"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"441","DOI":"10.3389\/fphys.2012.00441","article-title":"Contribution of oxidative stress to endothelial dysfunction in hypertension","volume":"3","author":"Silva","year":"2012","journal-title":"Front. Physiol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.tcm.2013.12.001","article-title":"Oxidative stress and endothelial dysfunction: Clinical evidence and therapeutic implications","volume":"24","author":"Higashi","year":"2014","journal-title":"Trends Cardiovasc. Med."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Fuccelli, R., Fabiani, R., and Rosignoli, P. (2018). Hydroxytyrosol Exerts Anti-Inflammatory and Anti-Oxidant Activities in a Mouse Model of Systemic Inflammation. Molecules, 23.","DOI":"10.3390\/molecules23123212"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.1016\/j.dld.2020.09.021","article-title":"Antioxidant activity of Hydroxytyrosol and Vitamin E reduces systemic inflammation in children with paediatric NAFLD","volume":"53","author":"Mosca","year":"2021","journal-title":"Dig. Liver Dis."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"912431","DOI":"10.1155\/2013\/912431","article-title":"Combined treatment of hydroxytyrosol with carbon monoxide-releasing molecule-2 prevents TNF \u03b1-induced vascular endothelial cell dysfunction through NO production with subsequent NF\u03baB inactivation","volume":"2013","author":"Zrelli","year":"2013","journal-title":"Biomed. Res. Int."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Serreli, G., Le Sayec, M., Diotallevi, C., Teissier, A., Deiana, M., and Corona, G. (2021). Conjugated Metabolites of Hydroxytyrosol and Tyrosol Contribute to the Maintenance of Nitric Oxide Balance in Human Aortic Endothelial Cells at Physiologically Relevant Concentrations. Molecules, 26.","DOI":"10.3390\/molecules26247480"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1589","DOI":"10.1007\/s10753-020-01242-9","article-title":"Role of Silent Information Regulator 1 (SIRT1) in Regulating Oxidative Stress and Inflammation","volume":"43","author":"Singh","year":"2020","journal-title":"Inflammation"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"2290","DOI":"10.18632\/aging.101068","article-title":"The protective role of Sirt1 in vascular tissue: Its relationship to vascular aging and atherosclerosis","volume":"8","author":"Kitada","year":"2016","journal-title":"Aging (Albany NY)"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.phymed.2018.09.208","article-title":"Hydroxytyrosol NO regulates oxidative stress and NO production through SIRT1 in diabetic mice and vascular endothelial cells","volume":"52","author":"Wang","year":"2019","journal-title":"Phytomedicine"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1089\/rej.2011.1245","article-title":"A diet rich in olive oil phenolics reduces oxidative stress in the heart of SAMP8 mice by induction of Nrf2-dependent gene expression","volume":"15","author":"Bayram","year":"2012","journal-title":"Rejuvenation Res."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1139\/cjpp-2016-0676","article-title":"Hydroxytyrosol regulates the autophagy of vascular adventitial fibroblasts through the SIRT1-mediated signaling pathway","volume":"96","author":"Wang","year":"2018","journal-title":"Can. J. Physiol Pharm."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1727","DOI":"10.1089\/ars.2017.7342","article-title":"Transcriptional Regulation by Nrf2","volume":"29","author":"Tonelli","year":"2018","journal-title":"Antioxid. Redox Signal."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"R83","DOI":"10.1530\/JOE-14-0662","article-title":"The role of Nrf2 in oxidative stress-induced endothelial injuries","volume":"225","author":"Chen","year":"2015","journal-title":"J. Endocrinol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.jare.2021.06.023","article-title":"Activation of Nrf2\/HO-1 signaling: An important molecular mechanism of herbal medicine in the treatment of atherosclerosis via the protection of vascular endothelial cells from oxidative stress","volume":"34","author":"Zhang","year":"2021","journal-title":"J. Adv. Res."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1002\/ptr.5339","article-title":"Role of Hydroxytyrosol-dependent Regulation of HO-1 Expression in Promoting Wound Healing of Vascular Endothelial Cells via Nrf2 De Novo Synthesis and Stabilization","volume":"29","author":"Zrelli","year":"2015","journal-title":"Phytother. Res."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.jnutbio.2018.03.014","article-title":"Peracetylated hydroxytyrosol, a new hydroxytyrosol derivate, attenuates LPS-induced inflammatory response in murine peritoneal macrophages via regulation of non-canonical inflammasome, Nrf2\/HO1 and JAK\/STAT signaling pathways","volume":"57","author":"Montoya","year":"2018","journal-title":"J. Nutr. Biochem."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"108984","DOI":"10.1016\/j.foodres.2020.108984","article-title":"Oleic acid and hydroxytyrosol present in olive oil promote ROS and inflammatory response in normal cultures of murine dermal fibroblasts through the NF-\u03baB and NRF2 pathways","volume":"131","author":"Saguie","year":"2020","journal-title":"Food Res. Int."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1016\/j.phymed.2013.05.002","article-title":"Oleuropein and oleacein may restore biological functions of endothelial progenitor cells impaired by angiotensin II via activation of Nrf2\/heme oxygenase-1 pathway","volume":"20","author":"Parzonko","year":"2013","journal-title":"Phytomedicine"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"4473","DOI":"10.1021\/jf104151d","article-title":"Hydroxytyrosol induces proliferation and cytoprotection against oxidative injury in vascular endothelial cells: Role of Nrf2 activation and HO-1 induction","volume":"59","author":"Zrelli","year":"2011","journal-title":"J. Agric. Food Chem."},{"key":"ref_102","unstructured":"de S Ribeiro, B.C., de C Faria, R.V., de S Nogueira, J., Valen\u00e7a, S.S., Chen, L., and Romana-Souza, B. (2022). Olive oil promotes the survival and migration of dermal fibroblasts through Nrf2 pathway activation. Lipids, online ahead of print."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"4006","DOI":"10.2174\/092986712802002536","article-title":"Anti-inflammatory effect of 3,4-DHPEA-EDA [2-(3,4 -hydroxyphenyl) ethyl (3S, 4E)-4-formyl-3-(2-oxoethyl)hex-4-enoate] on primary human vascular endothelial cells","volume":"19","author":"Sindona","year":"2012","journal-title":"Curr. Med. Chem."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"5789","DOI":"10.1039\/C9FO00586B","article-title":"The protective effect of hydroxytyrosol acetate against inflammation of vascular endothelial cells partly through the SIRT6-mediated PKM2 signaling pathway","volume":"10","author":"Yao","year":"2019","journal-title":"Food Funct."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"9086947","DOI":"10.1155\/2018\/9086947","article-title":"Hydroxytyrosol Ameliorates Endothelial Function under Inflammatory Conditions by Preventing Mitochondrial Dysfunction","volume":"2018","author":"Calabriso","year":"2018","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Karkovi\u0107 Markovi\u0107, A., Tori\u0107, J., Barbari\u0107, M., and Jakobu\u0161i\u0107 Brala, C. (2019). Hydroxytyrosol, Tyrosol and Derivatives and Their Potential Effects on Human Health. Molecules, 24.","DOI":"10.3390\/molecules24102001"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1016\/j.foodres.2017.11.053","article-title":"Hydroxytyrosol: Bioavailability, toxicity, and clinical applications","volume":"105","author":"Quiles","year":"2018","journal-title":"Food Res. Int."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1007\/s00394-015-1071-2","article-title":"Gender differences in plasma and urine metabolites from Sprague\u2013Dawley rats after oral administration of normal and high doses of hydroxytyrosol, hydroxytyrosol acetate, and DOPAC","volume":"56","author":"Ferreres","year":"2017","journal-title":"Eur. J. Nutr."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.jnutbio.2017.09.009","article-title":"Involvement of bilitranslocase and beta-glucuronidase in the vascular protection by hydroxytyrosol and its glucuronide metabolites in oxidative stress conditions","volume":"51","author":"Peyrol","year":"2018","journal-title":"J. Nutr. Biochem."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"2523","DOI":"10.1002\/mnfr.201500361","article-title":"Protective effect of hydroxytyrosol and its predominant plasmatic human metabolites against endothelial dysfunction in human aortic endothelial cells","volume":"59","author":"Pedret","year":"2015","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.jff.2017.11.007","article-title":"Hydroxytyrosol and its main plasma circulating metabolites attenuate the initial steps of atherosclerosis through inhibition of the MAPK pathway","volume":"40","author":"Motilva","year":"2018","journal-title":"J. Funct. Foods"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1002\/jcp.26600","article-title":"Acrolein-induced atherogenesis by stimulation of hepatic flavin containing monooxygenase 3 and a protection from hydroxytyrosol","volume":"234","author":"Wu","year":"2018","journal-title":"J. Cell. Physiol."},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Abate, M., Pisanti, S., Caputo, M., Citro, M., Vecchione, C., and Martinelli, R. (2020). 3-Hydroxytyrosol Promotes Angiogenesis In Vitro by Stimulating Endothelial Cell Migration. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21103657"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.fct.2013.04.045","article-title":"Hydroxytyrosyl alkyl ether derivatives inhibit platelet activation after oral administration to rats","volume":"58","author":"Reyes","year":"2013","journal-title":"Food Chem. Toxicol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1038\/sj.ejcn.1601917","article-title":"Bioavailability and antioxidant effects of olive oil phenols in humans: A review","volume":"58","author":"Vissers","year":"2004","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/j.jff.2016.12.033","article-title":"Effect of metabolites of hydroxytyrosol on protection against oxidative stress and inflammation in human endothelial cells","volume":"29","author":"Lopez","year":"2017","journal-title":"J. Funct. Foods"},{"key":"ref_117","doi-asserted-by":"crossref","unstructured":"Scoditti, E., Carpi, S., Massaro, M., Pellegrino, M., Polini, B., Carluccio, M.A., Wabitsch, M., Verri, T., Nieri, P., and De Caterina, R. (2019). Hydroxytyrosol Modulates Adipocyte Gene and miRNA Expression under Inflammatory Condition. Nutrients, 11.","DOI":"10.3390\/nu11102493"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1515\/biol-2021-0125","article-title":"3,4-Dihydroxyphenylethanol ameliorates lipopolysaccharide-induced septic cardiac injury in a murine model","volume":"16","author":"Zhang","year":"2021","journal-title":"Open Life Sci."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.atherosclerosis.2013.10.017","article-title":"Hydroxytyrosol suppresses MMP-9 and COX-2 activity and expression in activated human monocytes via PKC\u03b1 and PKC\u03b21 inhibition","volume":"232","author":"Scoditti","year":"2014","journal-title":"Atherosclerosis"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"703","DOI":"10.3892\/ijmm.2017.3078","article-title":"Assessment of the antioxidant activity of an olive oil total polyphenolic fraction and hydroxytyrosol from a Greek Olea europea variety in endothelial cells and myoblasts","volume":"40","author":"Kouka","year":"2017","journal-title":"Int. J. Mol. Med."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1021\/jf503357s","article-title":"Naturally occurring hydroxytyrosol derivatives: Hydroxytyrosyl acetate and 3,4-dihydroxyphenylglycol modulate inflammatory response in murine peritoneal macrophages. Potential utility as new dietary supplements","volume":"63","author":"Maya","year":"2015","journal-title":"J. Agric. Food Chem."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.redox.2016.10.006","article-title":"Hydroxytyrosol inhibits hydrogen peroxide-induced apoptotic signaling via labile iron chelation","volume":"10","author":"Kitsati","year":"2016","journal-title":"Redox Biol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1887","DOI":"10.1111\/ene.14360","article-title":"Exploratory study on immune phenotypes in Alzheimer\u2019s disease and vascular dementia","volume":"27","author":"Goldeck","year":"2020","journal-title":"Eur. J. Neurol."},{"key":"ref_124","doi-asserted-by":"crossref","unstructured":"Zhu, Y., Xian, X., Wang, Z., Bi, Y., Chen, Q., Han, X., Tang, D., and Chen, R. (2018). Research Progress on the Relationship between Atherosclerosis and Inflammation. Biomolecules, 8.","DOI":"10.3390\/biom8030080"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.jnutbio.2016.07.015","article-title":"Effects of hydroxytyrosol on cardiovascular biomarkers in experimental diabetes mellitus","volume":"37","author":"Reyes","year":"2016","journal-title":"J. Nutr. Biochem."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"753501","DOI":"10.3389\/fphys.2021.753501","article-title":"Sirtuin 6 Protects Against Oxidative Stress and Vascular Dysfunction in Mice","volume":"12","author":"Greiten","year":"2021","journal-title":"Front. Physiol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1016\/j.numecd.2021.12.020","article-title":"Sirt6 regulates autophagy in AGE-treated endothelial cells via KLF4","volume":"32","author":"Tong","year":"2022","journal-title":"Nutr. Metab. Cardiovasc. Dis."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.18632\/aging.100975","article-title":"SIRT6 protects against endothelial dysfunction and atherosclerosis in mice","volume":"8","author":"Xu","year":"2016","journal-title":"Aging (Albany NY)"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"e154217","DOI":"10.1172\/JCI154217","article-title":"Disruption of USP9X in macrophages promotes foam cell formation and atherosclerosis","volume":"132","author":"Wang","year":"2022","journal-title":"J. Clin. Investig."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"10992","DOI":"10.18632\/aging.102498","article-title":"Mangiferin promotes macrophage cholesterol efflux and protects against atherosclerosis by augmenting the expression of ABCA1 and ABCG1","volume":"11","author":"Ren","year":"2019","journal-title":"Aging (Albany NY)"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.jphs.2022.07.004","article-title":"HDL, cholesterol efflux, and ABCA1: Free from good and evil dualism","volume":"150","author":"Ogura","year":"2022","journal-title":"J. Pharm. Sci."},{"key":"ref_132","doi-asserted-by":"crossref","unstructured":"Summerhill, V.I., Grechko, A.V., Yet, S.-F., Sobenin, I.A., and Orekhov, A.N. (2019). The Atherogenic Role of Circulating Modified Lipids in Atherosclerosis. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20143561"},{"key":"ref_133","first-page":"5036572","article-title":"Hydroxytyrosol Plays Antiatherosclerotic Effects through Regulating Lipid Metabolism via Inhibiting the p38 Signal Pathway","volume":"2020","author":"Zhang","year":"2020","journal-title":"Biomed. Res. Int."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1016\/j.freeradbiomed.2021.06.017","article-title":"Beneficial effects of dietary supplementation with olive oil, oleic acid, or hydroxytyrosol in metabolic syndrome: Systematic review and meta-analysis","volume":"172","author":"Pastor","year":"2021","journal-title":"Free Radic. Biol. Med."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"14361","DOI":"10.1038\/ncomms14361","article-title":"The molecular basis of endothelial cell plasticity","volume":"8","author":"Dejana","year":"2017","journal-title":"Nat. Commun"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.jacc.2018.09.089","article-title":"Endothelial to Mesenchymal Transition in Cardiovascular Disease: JACC State-of-the-Art Review","volume":"73","author":"Kovacic","year":"2019","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1089\/dna.2017.3779","article-title":"Endothelial-to-Mesenchymal Transition: A Potential Mechanism for Atherosclerosis Plaque Progression and Destabilization","volume":"36","author":"Li","year":"2017","journal-title":"DNA Cell Biol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1002\/path.5574","article-title":"miRNA-200c-3p promotes endothelial to mesenchymal transition and neointimal hyperplasia in artery bypass grafts","volume":"253","author":"Chen","year":"2021","journal-title":"J. Pathol."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"112402","DOI":"10.1016\/j.yexcr.2020.112402","article-title":"MicroRNA-92a -mediated endothelial to mesenchymal transition controls vein graft neointimal lesion formation","volume":"398","author":"Zhong","year":"2021","journal-title":"Exp. Cell Res."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1124\/pharmrev.120.000096","article-title":"Endothelial Dysfunction in Atherosclerotic Cardiovascular Diseases and Beyond: From Mechanism to Pharmacotherapies","volume":"73","author":"Xu","year":"2021","journal-title":"Pharm. Rev."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"53","DOI":"10.3389\/fcvm.2020.00053","article-title":"Endothelial-to-Mesenchymal Transition, Vascular Inflammation, and Atherosclerosis","volume":"7","author":"Chen","year":"2020","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"4514","DOI":"10.1172\/JCI82719","article-title":"Endothelial-to-mesenchymal transition drives atherosclerosis progression","volume":"125","author":"Chen","year":"2015","journal-title":"J. Clin. Investig."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1007\/s00394-019-01920-x","article-title":"Targeting endothelial-to-mesenchymal transition: The protective role of hydroxytyrosol sulfate metabolite","volume":"59","author":"Terzuoli","year":"2020","journal-title":"Eur. J. Nutr."},{"key":"ref_144","doi-asserted-by":"crossref","unstructured":"Razali, R.A., Lokanathan, Y., Yazid, M.D., Ansari, A.S., Saim, A.B., and Hj Idrus, R.B. (2019). Modulation of Epithelial to Mesenchymal Transition Signaling Pathways by Olea Europaea and Its Active Compounds. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20143492"},{"key":"ref_145","doi-asserted-by":"crossref","unstructured":"Razali, R.A., Nik Ahmad Eid, N.A.H., Jayaraman, T., Amir Hassan, M.A., Azlan, N.Q., Ismail, N.F., Sainik, N.Q.A.V., Yazid, M.D., Lokanathan, Y., and Saim, A.B. (2018). The potential of Olea europaea extracts to prevent TGF\u03b21-induced epithelial to mesenchymal transition in human nasal respiratory epithelial cells. BMC Complement. Altern. Med., 18.","DOI":"10.1186\/s12906-018-2250-5"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"11853","DOI":"10.1038\/ncomms11853","article-title":"Endothelial to mesenchymal transition is common in atherosclerotic lesions and is associated with plaque instability","volume":"7","author":"Evrard","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1161\/CIRCRESAHA.119.314813","article-title":"Endothelial-to-Mesenchymal Transition","volume":"124","author":"Bischoff","year":"2019","journal-title":"Circ. Res."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"663266","DOI":"10.3389\/fphar.2021.663266","article-title":"Molecular Action of Hydroxytyrosol in Attenuation of Intimal Hyperplasia: A Scoping Review","volume":"12","author":"Vijakumaran","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1039\/C5FO00928F","article-title":"Hydroxytyrosol decreases the oxidative and nitrosative stress levels and promotes angiogenesis through HIF-1 independent mechanisms in renal hypoxic cells","volume":"7","author":"Calahorra","year":"2016","journal-title":"Food Funct."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"8826","DOI":"10.3892\/mmr.2017.7701","article-title":"Hydroxytyrosol contributes to cell proliferation and inhibits apoptosis in pulsed electromagnetic fields treated human umbilical vein endothelial cells in vitro","volume":"16","author":"Cheng","year":"2017","journal-title":"Mol. Med. Rep."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/978-981-15-3449-2_1","article-title":"Epigenetics in Health and Disease","volume":"1253","author":"Zhang","year":"2020","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_152","doi-asserted-by":"crossref","unstructured":"Leri, M., Scuto, M., Ontario, M.L., Calabrese, V., Calabrese, E.J., Bucciantini, M., and Stefani, M. (2020). Healthy Effects of Plant Polyphenols: Molecular Mechanisms. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21041250"},{"key":"ref_153","first-page":"17","article-title":"Epigenetic therapy-a new development in pharmacology","volume":"123","author":"Peedicayil","year":"2006","journal-title":"Indian J. Med. Res."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1038\/npp.2012.112","article-title":"DNA methylation and its basic function","volume":"38","author":"Moore","year":"2013","journal-title":"Neuropsychopharmacology"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"7885","DOI":"10.1111\/jcmm.14657","article-title":"Effect of oxidative stress and 3-hydroxytyrosol on DNA methylation levels of miR-9 promoters","volume":"23","author":"Cetrullo","year":"2019","journal-title":"J. Cell Mol. Med."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"4897","DOI":"10.1039\/C9FO01159E","article-title":"Identification and validation of common molecular targets of hydroxytyrosol","volume":"10","author":"Crespo","year":"2019","journal-title":"Food Funct."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"2039","DOI":"10.1093\/advances\/nmac067","article-title":"Nutri-Epigenetic Effects of Phenolic Compounds from Extra Virgin Olive Oil: A Systematic Review","volume":"13","author":"Visioli","year":"2022","journal-title":"Adv. Nutr."},{"key":"ref_158","unstructured":"Iqbal, A.M., and Jamal, S.F. (2022). StatPearls, StatPearls Publishing."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"e2160","DOI":"10.1097\/MD.0000000000002160","article-title":"High Blood Pressure and All-Cause and Cardiovascular Disease Mortalities in Community-Dwelling Older Adults","volume":"94","author":"Wu","year":"2015","journal-title":"Medicine"},{"key":"ref_160","doi-asserted-by":"crossref","unstructured":"Quir\u00f3s-Fern\u00e1ndez, R., L\u00f3pez-Plaza, B., Bermejo, L.M., Palma-Milla, S., and G\u00f3mez-Candela, C. (2019). Supplementation with Hydroxytyrosol and Punicalagin Improves Early Atherosclerosis Markers Involved in the Asymptomatic Phase of Atherosclerosis in the Adult Population: A Randomized, Placebo-Controlled, Crossover Trial. Nutrients, 11.","DOI":"10.3390\/nu11030640"},{"key":"ref_161","doi-asserted-by":"crossref","unstructured":"Hermans, M.P., Lempereur, P., Salembier, J.-P., Maes, N., Albert, A., Jansen, O., and Pincemail, J. (2020). Supplementation Effect of a Combination of Olive (Olea europea L.) Leaf and Fruit Extracts in the Clinical Management of Hypertension and Metabolic Syndrome. Antioxidants, 9.","DOI":"10.3390\/antiox9090872"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1007\/s00394-016-1188-y","article-title":"Impact of phenolic-rich olive leaf extract on blood pressure, plasma lipids and inflammatory markers: A randomised controlled trial","volume":"56","author":"Lockyer","year":"2017","journal-title":"Eur. J. Nutr."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1093\/ajh\/hpaa041","article-title":"Maternal Supplementation of Inositols, Fucoxanthin, and Hydroxytyrosol in Pregnant Murine Models of Hypertension","volume":"33","author":"Menichini","year":"2020","journal-title":"Am. J. Hypertens."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"111334","DOI":"10.1016\/j.biopha.2021.111334","article-title":"Link between microbiota and hypertension: Focus on LPS\/TLR4 pathway in endothelial dysfunction and vascular inflammation, and therapeutic implication of probiotics","volume":"137","author":"Grylls","year":"2021","journal-title":"Biomed. Pharm."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1089\/ars.2020.8112","article-title":"Oxidative Stress, GTPCH1, and Endothelial Nitric Oxide Synthase Uncoupling in Hypertension","volume":"34","author":"Wu","year":"2021","journal-title":"Antioxid. Redox Signal."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.1097\/HJH.0000000000000587","article-title":"Mechanisms and consequences of endothelial nitric oxide synthase dysfunction in hypertension","volume":"33","author":"Li","year":"2015","journal-title":"J. Hypertens."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1161\/HYPERTENSIONAHA.120.15856","article-title":"Nitric Oxide-cGMP Signaling in Hypertension: Current and Future Options for Pharmacotherapy","volume":"76","author":"Golshiri","year":"2020","journal-title":"Hypertension"},{"key":"ref_168","first-page":"29","article-title":"Highly potent antioxidant Olea europaea L. leaf extract affects carotid and renal haemodynamics in experimental hypertension: The role of oleuropein","volume":"17","author":"Ivanov","year":"2018","journal-title":"Excli J"},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1139\/cjpp-2020-0363","article-title":"Effects of oleuropein on rat's atria and thoracic aorta: A study of antihypertensive mechanisms","volume":"99","author":"Ilic","year":"2021","journal-title":"Can. J. Physiol. Pharm."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1016\/j.redox.2014.07.001","article-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","volume":"2","author":"Storniolo","year":"2014","journal-title":"Redox Biol."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"1398","DOI":"10.1017\/S0007114509993485","article-title":"Physiological concentrations of dietary polyphenols regulate vascular endothelial cell expression of genes important in cardiovascular health","volume":"103","author":"Nicholson","year":"2010","journal-title":"Br. J. Nutr."},{"key":"ref_172","doi-asserted-by":"crossref","unstructured":"Lu, C.L., Liao, M.T., Hou, Y.C., Fang, Y.W., Zheng, C.M., Liu, W.C., Chao, C.T., Lu, K.C., and Ng, Y.Y. (2020). Sirtuin-1 and Its Relevance in Vascular Calcification. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21051593"},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.freeradbiomed.2022.06.003","article-title":"SIRT1 exerts anti-hypertensive effect via FOXO1 activation in the rostral ventrolateral medulla","volume":"188","author":"Ren","year":"2022","journal-title":"Free Radic. Biol. Med."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.vph.2016.12.003","article-title":"G004, a synthetic sulfonylurea compound, exerts anti-atherosclerosis effects by targeting SIRT1 in ApoE(-\/-) mice","volume":"89","author":"Qian","year":"2017","journal-title":"Vasc. Pharm."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1080\/09637480500539420","article-title":"Blood pressure lowering effect of olive is mediated through calcium channel blockade","volume":"56","author":"Gilani","year":"2005","journal-title":"Int. J. Food Sci. Nutr."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.jep.2008.08.018","article-title":"Olea europaea leaf extract exerts L-type Ca2+ channel antagonistic effects","volume":"120","author":"Scheffler","year":"2008","journal-title":"J. Ethnopharmacol."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1111\/bcpt.13426","article-title":"Ageing and longevity genes in cardiovascular diseases","volume":"127","author":"Liberale","year":"2020","journal-title":"Basic Clin. Pharm. Toxicol."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1161\/CIRCRESAHA.118.311378","article-title":"Mechanisms of Vascular Aging","volume":"123","author":"Ungvari","year":"2018","journal-title":"Circ. Res."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1136\/pgmj.2005.036053","article-title":"Ageing and vascular ageing","volume":"82","author":"Jani","year":"2006","journal-title":"Postgrad. Med. J."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.jphs.2015.09.002","article-title":"Vascular nitric oxide: Beyond eNOS","volume":"129","author":"Zhao","year":"2015","journal-title":"J. Pharmacol. Sci."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.exger.2017.06.007","article-title":"Vascular ageing: Underlying mechanisms and clinical implications","volume":"109","author":"Laina","year":"2018","journal-title":"Exp. Gerontol."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"757","DOI":"10.2147\/CIA.S158513","article-title":"Oxidative stress, aging, and diseases","volume":"13","author":"Liguori","year":"2018","journal-title":"Clin. Interv. Aging"},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1016\/j.exger.2011.07.006","article-title":"Serum biomarkers of aging in the Brown Norway rat","volume":"46","author":"Gordon","year":"2011","journal-title":"Exp. Gerontol."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1046\/j.1365-2249.2003.02137.x","article-title":"Predicting death from tumour necrosis factor-alpha and interleukin-6 in 80-year-old people","volume":"132","author":"Bruunsgaard","year":"2003","journal-title":"Clin. Exp. Immunol."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1248\/bpb.32.578","article-title":"Suppressive Effects of Hydroxytyrosol on Oxidative Stress and Nuclear Factor-kappaB Activation in THP-1 Cells","volume":"32","author":"Zhang","year":"2009","journal-title":"Biol. Pharm. Bull."},{"key":"ref_186","doi-asserted-by":"crossref","unstructured":"Brunetti, G., Di Rosa, G., Scuto, M., Leri, M., Stefani, M., Schmitz-Linneweber, C., Calabrese, V., and Saul, N. (2020). Healthspan Maintenance and Prevention of Parkinson\u2019s-like Phenotypes with Hydroxytyrosol and Oleuropein Aglycone in C. elegans. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21072588"},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"2331","DOI":"10.1002\/mnfr.201600332","article-title":"Hydroxytyrosol mildly improve cognitive function independent of APP processing in APP\/PS1 mice","volume":"60","author":"Peng","year":"2016","journal-title":"Mol. Nutr. Food Res."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/4\/1861\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:37:26Z","timestamp":1760121446000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/4\/1861"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,16]]},"references-count":187,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["molecules28041861"],"URL":"https:\/\/doi.org\/10.3390\/molecules28041861","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,16]]}}}