{
  "abstract": "Background: Venous intimal hyperplasia remains a major cause of saphenous vein graft failure following coronary artery bypass grafting Current antiproliferative strategies often impair endothelial cell function, exacerbating vascular injury. Hydroxytyrosol (HT), a bioactive olive phenolic compound, exhibits antioxidant and anti-inflammatory properties, but its coordinated effects on vascular smooth muscle cells and ECs remain unclear.\n\nMethods: Primary human saphenous vein-derived SMCs and ECs were exposed to graded concentrations of HT to evaluate cell viability, proliferation, migration, chemotaxis, and signalling responses. A human saphenous vein ring (hSVR) culture model was used to investigate the effects of HT on spontaneous ex vivo intimal hyperplasia.\n\nResults: HT (20–320 μM) significantly inhibited PDGF-BB-induced SMC proliferation, migration, and chemotaxis accompanied by reduced Akt signalling. In contrast, HT at concentrations ≤50 μM did not produce a statistically significant reduction in EC viability, proliferation, and migration while activating the Nrf2/HO-1 antioxidant pathway. In the ex vivo hSVR model, 50 μM HT reduced intimal thickness by 45.2% and significantly attenuated neointimal cell proliferation at day 21. HT also suppressed Akt activation, enhanced HO-1 expression, and reduced vimentin expression, consistent with attenuation of vascular remodeling. Attempts to evaluate re-endothelialization were inconclusive because seeded ECs failed to establish continuous luminal coverage in the ex vivo model.\n\nConclusion: Hydroxytyrosol selectively inhibits SMC activation while preserving endothelial homeostasis associated with differential modulation of the Akt and Nrf2/HO-1 pathways. These findings demonstrate that HT effectively attenuates intimal hyperplasia in a human ex vivo vein model and support its potential as an adjunctive strategy for improving vein graft patency. Further studies using perfused vascular systems or in vivo models are required to determine its effects on endothelial repair and re-endothelialisation.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Tissue Engineering and Regenerative Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia",
    "Institute of Medical Science Technology, Universiti Kuala Lumpur (UniKL)",
    "Cardiovascular and Pulmonary (CardioResp) Research Group, Universiti Kebangsaan Malaysia",
    "Cardiovascular Translational Research. Navarrabiomed (Fundación Miguel Servet), Instituto de Investigación Sanitaria de Navarra (IdiSNA), Hospital Universitario de Navarra (HUN), Universidad Pública de Navarra (UPNA)",
    "Pusat Jantung Dan Paru-Paru, Hospital Canselor Tuanku Muhriz, Jalan Yaacob Latif, Bandar Tun Razak",
    "Department of Surgery, Faculty of Medicine, Universiti Kebangsaan Malaysia"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Ubashini Vijakumaran"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Muhammad Dain Yazid"
    },
    {
      "affs": [
        3
      ],
      "name": "Eva Jover"
    },
    {
      "affs": [
        4,
        5
      ],
      "name": "Nur Ayub Md Ali"
    },
    {
      "affs": [
        4,
        5
      ],
      "name": "Hairulfaizi Haron"
    },
    {
      "affs": [
        2,
        5
      ],
      "name": "Muhammad Ishamuddin Ismail"
    },
    {
      "affs": [
        4,
        5
      ],
      "name": "Mohd Ramzisham Abdul Rahman"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Nadiah Sulaiman"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/cem0tz1sj441s.bib",
  "cited_by": 0,
  "doi": "10.3389/fphar.2026.1962884",
  "fulltext_url": null,
  "id": "cem0tz1sj441s",
  "issns": [
    "1663-9812"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fphar.2026.1962884/full",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2746|Cardiac and Coronary Surgery Techniques"
    ]
  ],
  "openalex": "W7224136761",
  "pdf_url": "https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2026.1962884/pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-28",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/cem0tz1sj441s.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:06Z",
      "native_id": "10.3389/fphar.2026.1962884",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fphar.2026.1962884/full"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2746|Cardiac and Coronary Surgery Techniques",
      "subfield": "surgery"
    }
  ],
  "title": "Hydroxytyrosol attenuates intimal hyperplasia in in vitro and ex vivo human saphenous vein models: association with Akt and Nrf2/HO-1 signalling",
  "title_text": "Hydroxytyrosol attenuates intimal hyperplasia in in vitro and ex vivo human saphenous vein models: association with Akt and Nrf2/HO-1 signalling",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:20:06Z",
  "url": "https://research.draconitic.com/paper/cem0tz1sj441s",
  "venue": "Frontiers in Pharmacology",
  "versions": []
}