{
  "abstract": "Background: Respiratory exposure to fine particulate matter (PM2.5), including diesel exhaust particles (DEPs), is a major air pollutant associated with pulmonary inflammation and cardiovascular diseases. This study investigated the protective effects and underlying mechanisms of retinoic acid (RA) against PM2.5-induced lung injury and accelerated atherosclerosis. Methods: Differentially expressed genes (DEGs) were identified from lung tissues of five non-smokers and six patients with chronic obstructive pulmonary disease obtained from the Gene Expression Omnibus (GEO) database and analyzed using the L1000CDS2, which identified RA as a candidate therapeutic compound. The Comparative Toxicogenomics Database was subsequently used to investigate curated associations between lung and cardiovascular disorders, suggesting the endothelial nitric oxide synthase (eNOS)/nitric oxide (NO) signaling pathway as a candidate mechanism for experimental validation. ApoE−/− mice were exposed to DEP via a nebulization chamber and treated orally with all-trans retinoic acid (1 or 5 mg/kg/day) for 8 weeks. Results: RA significantly reduced C-X-C motif chemokine ligand 1/2 (CXCL1/2) levels in bronchoalveolar lavage fluid and decreased pulmonary expression of Muc5ac, IL-1β, IL-6, and TNF-α. RA also lowered blood pressure, improved serum lipid profiles, and attenuated inflammatory cell infiltration and arterial wall thickening in the thoracic aorta. In HUVECs, RA significantly increased guanosine triphosphate (GTP) cyclohydrolase-1 (GTPCH-1) expression, eNOS phosphorylation, tetrahydrobiopterin (BH4) levels, and the BH4/BH2 ratio. Conclusion: These findings suggest that the activation of the GTPCH-1/BH4/eNOS coupling pathway contributes to the protective effects of RA against DEP-induced cardiovascular injury.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Oriental Pharmacy, College of Pharmacy, Wonkwang University, Iksan 54538, Republic of Korea",
    "Wonkwang-Oriental Medicines Research Institute, Wonkwang University, Iksan 54538, Republic of Korea",
    "Hanbang Cardio-Renal Syndrome Research Center, Wonkwang University, 460, Iksan-daero, Iksan 54538, Republic of Korea"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Ji-Ye Han"
    },
    {
      "affs": [
        2
      ],
      "name": "Byung Hyuk Han"
    },
    {
      "affs": [
        2
      ],
      "name": "Se Hoon Jang"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Bori Lee"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Young-Mi Lee"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Yun Jung Lee",
      "orcid": "0000-0002-9347-8606"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/d04vqtmy8t3wd.bib",
  "cited_by": 0,
  "doi": "10.3390/nu18213680",
  "fulltext_url": null,
  "id": "d04vqtmy8t3wd",
  "issns": [
    "2072-6643"
  ],
  "landing_url": "https://www.mdpi.com/2072-6643/18/21/3680",
  "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": null,
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-06",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/d04vqtmy8t3wd.ris",
  "sources": [
    {
      "first_seen": "2026-11-06T12:21:20Z",
      "native_id": "10.3390/nu18213680",
      "source": "crossref",
      "url": "https://www.mdpi.com/2072-6643/18/21/3680"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "issn:2072-6643",
      "subfield": "nutrition"
    }
  ],
  "title": "Retinoic Acid Alleviates Accelerated Atherosclerosis in Diesel Exhaust–Derived PM2.5–Exposed ApoE−/− Mice by Enhancing eNOS–NO Coupling",
  "title_text": "Retinoic Acid Alleviates Accelerated Atherosclerosis in Diesel Exhaust–Derived PM2.5–Exposed ApoE−/− Mice by Enhancing eNOS–NO Coupling",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T00:23:00Z",
  "url": "https://research.draconitic.com/paper/d04vqtmy8t3wd",
  "venue": "Nutrients",
  "versions": []
}