{
  "id": 16502869,
  "title": "Erythrocyte extravasation drives ferroptosis and inflammatory amplification in eccentric contraction-induced skeletal muscle injury via the heme-HO-1-iron axis",
  "url": "https://urgent.news/2026/10/25/erythrocyte-extravasation-drives-ferroptosis-and-inflammatory",
  "topic": "science",
  "section": "Science",
  "published": "2026-10-25T00:00:00.000Z",
  "source": {
    "name": "bioRxiv",
    "slug": "biorxiv",
    "url": "https://www.biorxiv.org/content/10.64898/2026.10.21.760722v1?rss=1"
  },
  "original_language": "en",
  "account": "Erythrocyte extravasation following eccentric contraction-induced skeletal muscle injury plays a pivotal role in driving ferroptosis and amplifying inflammation, according to a recent study. This condition, often encountered in sports-related injuries, is marked by pain, reduced muscle function, sluggish recovery, and a propensity for recurring injuries. Despite its prevalence, treatment options remain primarily symptomatic, and there is a dearth of mechanism-based therapeutic targets. Microvascular disruption and erythrocyte extravasation are hallmarks of severe muscle strain, yet the metabolic consequences of extravasated erythrocytes have been largely unexplored. In the context of hemorrhagic and hemolytic conditions, heme released by erythrocytes can activate heme oxygenase-1 (HO-1) leading to iron release and ferroptosis, a form of cell death that could potentially exacerbate inflammation. However, the involvement of this pathway in eccentric muscle injury has remained a subject of uncertainty. To unravel this mystery, researchers employed a parameter-controlled rat model, where the gastrocnemius muscle underwent controlled eccentric stretch repetitions ranging from 0 to 150. The study assessed various parameters including muscle torque, gait, weight-bearing capacity, endurance, pain threshold, histopathology, microcirculatory perfusion, macrophage polarization, and levels of heme, ferrous iron, glutathione (GSH), malondialdehyde (MDA), glutathione peroxidase 4 (GPX4), and pro-inflammatory cytokines. As the number of repetitions increased, there was a discernible decline in functional performance and an uptick in myofiber damage, erythrocyte extravasation, inflammatory cell infiltration, and microcirculatory disturbances. Concurrently, there was an increase in heme levels, activation of HO-1 in perivascular macrophages, accumulation of muscle iron, depletion of GSH and GPX4, elevation of MDA, and heightened M1 macrophage activity and cytokine production. These findings suggest a potential pathway involving heme, HO-1, iron, and ferroptosis that contributes to inflammation in eccentric muscle injury. This insight not only opens avenues for mechanistic validation but also paves the way for the development of targeted therapies. Keywords: Eccentric contraction-induced muscle injury; Erythrocyte extravasation; Heme oxygenase-1; Ferroptosis; Macrophage polarization.",
  "summary": "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…",
  "key_points": [],
  "editors_take": null,
  "illustration": null,
  "coverage": {
    "outlets": 1,
    "also_reported_by": []
  },
  "ai_generated": true,
  "disclaimer": "Summaries, key points and the editor’s take are written by software from other outlets’ reporting and may contain errors — always check the linked original."
}