{
  "abstract": "Background and Aims. Patients with type 2 diabetes mellitus (T2D) exhibit enhanced platelet reactivity and an increased risk of atherothrombotic events. Although low‑dose acetylsalicylic acid (ASA) irreversibly inhibits cyclooxygenase‑1, a substantial proportion of patients with T2D show a suboptimal antiplatelet response. Oxidative stress has been proposed as a key mechanism underlying this variability. The aim of this study was to investigate the relationship between oxidative stress–related pathways, platelet function, and ASA responsiveness in patients with T2D, focusing on platelet heme oxygenase‑1 (HO‑1) and platelet‑associated microRNAs (miRNAs). Methods. Patients with T2D receiving chronic ASA therapy (T2D+ASA, n = 55), patients with T2D not receiving ASA (T2D, n = 11), and subjects without T2D (NOT2D, n = 20) were enrolled. Chronic ASA therapy consisted of 100 mg/day for at least one month. Blood and urine samples were collected for platelet isolation and biochemical analyses. Patients in the T2D+ASA group were stratified into tertiles according to platelet HO‑1 levels (Figure 1A). Platelet miRNA expression profiles were identified by next‑generation sequencing and validated by real‑time PCR. KEGG pathway enrichment analysis was performed on differentially expressed platelet‑associated miRNAs. Results. Platelet HO‑1 levels differed significantly among groups. Patients with T2D, regardless of ASA treatment, exhibited significantly lower platelet HO‑1 levels compared with NOT2D subjects (both P < 0.001), Figure 1B. Among T2D+ASA patients, lower platelet HO‑1 levels were associated with higher levels of markers of platelet activation, including serum thromboxane B₂ (first vs third tertile, P = 0.036) and urinary 11‑dehydro‑thromboxane B₂ (P = 0.030), Figure 1C-D. A total of 62 platelet‑associated miRNAs were identified. Reduced expression of hsa‑let‑7b‑5p, hsa‑miR‑98‑5p, hsa‑miR‑423‑5p, hsa‑miR‑652‑3p, and hsa‑miR‑625‑5p, and increased expression of hsa‑miR‑21‑5p, hsa‑miR‑23a‑3p, hsa‑miR‑126‑5p, hsa‑miR‑150‑5p, hsa‑miR‑151a‑3p, and hsa‑miR‑200c‑3p were observed in patients with lower HO‑1 levels, Figure 1E-F. KEGG analysis revealed enrichment of pathways related to platelet activation, fluid shear stress, and atherosclerosis. Conclusions. Patients with T2D exhibit reduced platelet HO‑1 levels independently of chronic low‑dose ASA therapy, indicating a persistent impairment of platelet antioxidant capacity that may contribute to enhanced platelet reactivity and reduced responsiveness to antiplatelet treatment. In this clinical context, lower HO‑1 levels are associated with a reduced expression of regulatory let‑7 family members, including hsa‑let‑7b‑5p and hsa‑miR‑98‑5p, suggesting a failure of compensatory mechanisms linking platelet miRNAs to redox‑sensitive pathways, potentially due to insufficient repression of the HMOX1 transcriptional inhibitor Bach1. Consistently, platelet‑associated miRNA profiling and KEGG pathway analysis indicate that low HO‑1 levels are associated with a less adaptive modulation of platelet activation and platelet–vascular signaling pathways, which may translate into suboptimal antiplatelet responses and an increased risk of atherothrombotic events.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 1,
  "authors": [
    {
      "name": "Rossella Liani"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/9bhrqt350jwjb.bib",
  "cited_by": 0,
  "doi": null,
  "fulltext_url": "https://www.btvb.org/btvb/article/view/749",
  "id": "9bhrqt350jwjb",
  "issns": [
    "2785-5309"
  ],
  "landing_url": "https://www.btvb.org/btvb/article/view/749",
  "language": "en",
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "RC666-701"
    ]
  ],
  "openalex": null,
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-26",
  "publisher": "PAGEPress Publications",
  "ris": "https://research.draconitic.com/paper/9bhrqt350jwjb.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:47:32Z",
      "native_id": "9e0c504b2cd74bfc81e62299f3569fe6",
      "source": "doaj",
      "url": "https://www.btvb.org/btvb/article/view/749"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "lcc:RC666-701",
      "subfield": "cardiovascular"
    }
  ],
  "title": "CO047 | OXIDATIVE STRESS–RELATED PLATELET HO-1 AND MICRO-RNA MODULATION IN PATIENTS WITH TYPE 2 DIABETES MELLITUS UNDER ASPIRIN THERAPY",
  "title_text": "CO047 | OXIDATIVE STRESS–RELATED PLATELET HO-1 AND MICRO-RNA MODULATION IN PATIENTS WITH TYPE 2 DIABETES MELLITUS UNDER ASPIRIN THERAPY",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:47:32Z",
  "url": "https://research.draconitic.com/paper/9bhrqt350jwjb",
  "venue": "Bleeding, Thrombosis and Vascular Biology",
  "versions": []
}