{
  "abstract": "Eccentric contraction-induced skeletal muscle injury is a common sports-related condition characterized by pain, impaired muscle function, slow recovery, and frequent recurrence, yet treatment remains symptomatic and mechanism-based targets are lacking. Although microvascular disruption and erythrocyte extravasation characterize severe muscle strain, the metabolic fate of extravasated erythrocytes has received little attention. In hemorrhagic and hemolytic conditions, erythrocyte-derived heme can activate heme oxygenase-1 (HO-1)-mediated iron release and ferroptosis, potentially amplifying inflammation; however, whether this pathway contributes to eccentric muscle injury remains unknown. To address this gap, we established a parameter-controlled rat model in which the gastrocnemius underwent 0, 50, 100, or 150 eccentric stretch repetitions. Muscle torque, gait, weight-bearing, endurance, pain threshold, histopathology, microcirculatory perfusion, macrophage polarization, and heme, ferrous iron, glutathione (GSH), malondialdehyde (MDA), glutathione peroxidase 4 (GPX4), and pro-inflammatory cytokine levels were assessed. Increasing repetitions produced graded functional impairment, myofiber damage, erythrocyte extravasation, inflammatory infiltration, and microcirculatory disturbance. Heme accumulation was accompanied by HO-1 upregulation in perivascular CD68-positive (CD68) macrophages, muscle iron accumulation, GSH and GPX4 depletion, elevated MDA, and increased M1 macrophage and cytokine levels. These findings suggest a potential heme-HO-1-iron-ferroptosis-associated inflammatory mechanism in eccentric muscle injury, providing a rationale for mechanistic validation and targeted therapeutic development. Keywords: Eccentric contraction-induced muscle injury; Erythrocyte extravasation; Heme oxygenase-1; Ferroptosis; Macrophage polarization",
  "abstract_shown": true,
  "affiliations": [
    "Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "name": "M. Liu"
    },
    {
      "affs": [
        0
      ],
      "name": "X. Wang"
    },
    {
      "name": "Z. Liu"
    },
    {
      "name": "F. You"
    },
    {
      "name": "Q. Shen"
    },
    {
      "name": "M. Zhang"
    },
    {
      "name": "S. Chen"
    },
    {
      "name": "Y. Jing"
    },
    {
      "name": "J. Yang"
    },
    {
      "affs": [
        0
      ],
      "name": "Y. Wang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6mbed6rhd6dg8.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.21.760722",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.21.760722v1.full",
  "id": "6mbed6rhd6dg8",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.21.760722v1",
  "language": null,
  "licence": "CC-BY-ND",
  "licence_label": "CC BY-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "immunology"
    ],
    [
      "openalex",
      "2742|Exercise and Physiological Responses"
    ]
  ],
  "openalex": "W7223552009",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.21.760722v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-21",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/6mbed6rhd6dg8.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:29:35Z",
      "native_id": "10.64898/2026.10.21.760722",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.21.760722v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:immunology",
      "subfield": "immunology"
    }
  ],
  "title": "Erythrocyte extravasation drives ferroptosis and inflammatory amplification in eccentric contraction-induced skeletal muscle injury via the heme-HO-1-iron axis",
  "title_text": "Erythrocyte extravasation drives ferroptosis and inflammatory amplification in eccentric contraction-induced skeletal muscle injury via the heme-HO-1-iron axis",
  "type": "preprint",
  "updated_at": "2026-10-30T12:29:35Z",
  "url": "https://research.draconitic.com/paper/6mbed6rhd6dg8",
  "venue": "bioRxiv",
  "versions": []
}