ArticleImmunity, inflammation and disease2026
Mast Cell-Derived CXCL4: A Key Mediator of Ferroptosis and Cardiac Damage in Septic Cardiomyopathy.
Article in Immunity, inflammation and disease, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
2 citing papers in PubMed.
- Mast Cell-Derived CXCL4: A Key Mediator of Ferroptosis and Cardiac Damage in Septic Cardiomyopathy.Immunity, inflammation and disease · 2026Article
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors.
Funding
Abstract
backgroundSeptic cardiomyopathy (SCM) is a common and life-threatening complication of severe sepsis, with high mortality due to unclear underlying mechanisms. CXCL4, a key pro-inflammatory factor, is implicated in various heart diseases, while ferroptosis (iron and lipid hydrogen peroxide-dependent regulated cell death) plays a crucial role in SCM progression. However, the specific crosstalk between CXCL4, ferroptosis, and SCM remains unelucidated.
methodsBALB/c mice were randomly divided into six groups (Control, LPS, LPS + Sodium Cromoglycate (CS), LPS + Ferrostatin-1 (Fer-1), LPS + Pifithrin-α (PFT-α), LPS + Niclosamide) to establish the SCM model via intraperitoneal LPS injection. In vivo experiments included histopathological examination (H&E, toluidine blue staining), survival analysis, ELISA, Western blot, immunofluorescence, immunohistochemistry, TUNEL staining, and detection of myocardial markers (CK-MB, AST, LDH) and oxidative stress indicators (SOD, MDA, iron content). In vitro, RAW264.7 macrophages were treated with CXCL4 alone or combined with inhibitors (Fer-1, PFT-α, Niclosamide), followed by CCK-8 assay, ROS detection, qRT-PCR, Western blot, and phagocytosis microbead assay.
resultsIn vivo, SCM mice exhibited significantly elevated CXCL4 levels in serum and heart tissue, accompanied by mast cell activation and degranulation. Inhibiting mast cell activation (with CS) reduced CXCL4 production, alleviated cardiac inflammation and ferroptosis (increased SLC7A11/GPX4 expression, decreased 4-HNE), and improved survival. TUNEL staining revealed predominant macrophage death in SCM hearts. In vitro, CXCL4 induced macrophage ferroptosis (downregulated SLC7A11/GPX4) and impaired phagocytic function (reduced CD36/MERTK expression), which was reversed by Fer-1. Mechanistically, CXCL4 activated STAT3 phosphorylation, regulating downstream P53; inhibiting STAT3 (Niclosamide) or P53 (PFT-α) alleviated macrophage ferroptosis, restored phagocytosis, and mitigated cardiac injury in SCM mice.
conclusionMast cell-derived CXCL4 induces macrophage ferroptosis via the STAT3/P53 signaling pathway, impairs macrophage phagocytic function, and exacerbates myocardial injury in SCM. Targeting mast cell activation, CXCL4 release, or the STAT3/P53-ferroptosis axis may serve as promising therapeutic strategies for SCM. CLINICAL TRIAL NUMBER: Not applicable.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.