{
  "abstract": "Despite advances in lipid lowering, anti-inflammatory therapy and revascularization, residual cardiovascular risk may partly reflect persistent lesion-level inflammation and defective plaque repair that are not fully corrected by systemic risk-factor control. The mechanistic target of rapamycin (mTOR) integrates inflammatory, metabolic and reparative programmes, but its effects vary with cell state, plaque niche, complex identity, and signalling amplitude and duration. Evidence is strongest for context-dependent macrophage mTOR signalling, yet macrophage/myeloid mTORC2 disruption has produced opposing lesion phenotypes across genetic models; endothelial and smooth-muscle evidence remains less direct. Pharmacological, genetic and lesion-directed delivery studies demonstrate that mTOR perturbation can modify experimental atherosclerosis. However, genetic perturbation cannot be equated with rapalog pharmacology, and existing studies do not yet define cell-resolved exposure–engagement–response relationships and relate them to plaque composition. This evidential asymmetry limits interpretation of whether broad or prolonged mTOR inhibition can selectively suppress disease-amplifying outputs while preserving homeostatic programmes. In this Review, focused primarily on lipid-rich, rupture-prone plaques and using rapalogs as the principal pharmacological model, we apply an exposure-guided pharmacological framework to distinguish administered dose from lesion exposure, cellular availability, target engagement and pharmacodynamic recovery. Compartment-resolved PK–PD studies, cell-specific pathway interrogation and large-animal validation will be needed to quantify these relationships and determine whether maladaptive mTOR outputs can be suppressed without compromising vascular repair.",
  "abstract_shown": true,
  "affiliations": [
    "Key Laboratory of Model Animals and Stem Cell Biology in Hunan Province, Health Science Center, Hunan Normal University",
    "Health Management Center, Hengyang Central Hospital Affiliated to Hunan Normal University",
    "Aging Health Research Center, School of Nursing, Health Science Center, Hunan Normal University"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Ruoyu Han"
    },
    {
      "affs": [
        0
      ],
      "name": "Mao Peng"
    },
    {
      "affs": [
        0
      ],
      "name": "Zihang Song"
    },
    {
      "affs": [
        0
      ],
      "name": "Yifan Tang"
    },
    {
      "affs": [
        0
      ],
      "name": "Ziyi Yao"
    },
    {
      "affs": [
        0
      ],
      "name": "Yan She"
    },
    {
      "affs": [
        0
      ],
      "name": "Shuhan Cheng"
    },
    {
      "affs": [
        1
      ],
      "name": "Xiaomin Li"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Pingping He"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/7h2s812jgqm1f.bib",
  "cited_by": 0,
  "doi": "10.3389/fphar.2026.1994231",
  "fulltext_url": null,
  "id": "7h2s812jgqm1f",
  "issns": [
    "1663-9812"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fphar.2026.1994231/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",
      "2403|Atherosclerosis and Cardiovascular Diseases"
    ]
  ],
  "openalex": "W7223709573",
  "pdf_url": "https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2026.1994231/pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-26",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/7h2s812jgqm1f.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:06Z",
      "native_id": "10.3389/fphar.2026.1994231",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fphar.2026.1994231/full"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2403|Atherosclerosis and Cardiovascular Diseases",
      "subfield": "immunology"
    }
  ],
  "title": "Context-dependent mTOR pharmacology in atherosclerotic plaque stability and exposure-guided modulation",
  "title_text": "Context-dependent mTOR pharmacology in atherosclerotic plaque stability and exposure-guided modulation",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:20:06Z",
  "url": "https://research.draconitic.com/paper/7h2s812jgqm1f",
  "venue": "Frontiers in Pharmacology",
  "versions": []
}