ArticleESC heart failure2020
Reactive fibrosis precedes doxorubicin-induced heart failure through sterile inflammation.
Article in ESC heart failure, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 2 of them syntheses that pooled it.
What it found
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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
46 citing papers in PubMed, 2 syntheses or guidelines pooled it, 72 citations in OpenAlex.
- Efficacy of Physical Exercise to Offset Anthracycline-Induced Cardiotoxicity: A Systematic Review and Meta-Analysis of Clinical and Preclinical Studies.Journal of the American Heart Association · 2021Pooled it
- Extracellular matrix remodeling in animal models of anthracycline-induced cardiomyopathy: a meta-analysis.Journal of molecular medicine (Berlin, Germany) · 2021Pooled it
- Doxorubicin exposure leads to cardiac fibroblast dysregulation and worsens fibrotic remodeling in the pathological heart.Journal of molecular and cellular cardiology plus · 2026Article
- Endothelial Transcription Factor EB Protects Against Doxorubicin-Induced Endothelial Toxicity and Cardiac Dysfunction.Circulation · 2026Article
- Chemo-/radiotherapy-induced cardiomyopathy: roles of mitochondria and endoplasmic reticulum.Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] · 2026Review
- Macrophage surface protein Mac-2 mediates inflammatory and stromal stress pathways in doxorubicin-induced cardiac injury.Cardio-oncology (London, England) · 2026Article
- Sustained mesenchymal reprogramming of endothelial cells after completion of chemotherapy.Cardio-oncology (London, England) · 2025Article
- Nanomedicine-Based Strategies for Mitigating Chemo/Radiotherapy-Induced Cardiac Inflammation and Fibrosis.Cardiovascular toxicology · 2025Review
- Temporal Dynamics of Extracellular Matrix Remodeling in Anthracycline-Induced Cardiotoxicity.Cells · 2025Review
- Doxorubicin-Induced Cardiotoxicity: A Comprehensive Update.Journal of cardiovascular development and disease · 2025Review
- The Protective Effects of Carvacrol Against Doxorubicin-Induced Cardiotoxicity In Vitro and In Vivo.Cardiovascular toxicology · 2025Article
- The key players of inflammasomes and pyroptosis in sepsis-induced pathogenesis and organ dysfunction.Frontiers in pharmacology · 2025Review
- Article
- The Role of MicroRNAs in the Pathogenesis of Doxorubicin-Induced Vascular Remodeling.International journal of molecular sciences · 2024Review
- α-Bisabolol: A Dietary Sesquiterpene that Attenuates Apoptotic and Nonapoptotic Cell Death Pathways by Regulating the Mitochondrial Biogenesis and Endoplasmic Reticulum Stress-Hippo Signaling Axis in Doxorubicin-Induced Acute Cardiotoxicity in Rats.ACS pharmacology & translational science · 2024Article
- The significance of the apelinergic system in doxorubicin-induced cardiotoxicity.Heart failure reviews · 2024Review
- Navigating cancer therapy induced cardiotoxicity: From pathophysiology to treatment innovations.Advanced drug delivery reviews · 2024Review
- Cytotoxic T cells drive doxorubicin-induced cardiac fibrosis and systolic dysfunction.Nature cardiovascular research · 2024Article
- Characterization of systolic and diastolic function, alongside proteomic profiling, in doxorubicin-induced cardiovascular toxicity in mice.Cardio-oncology (London, England) · 2024Article
- Extracellular vesicles derived from HuMSCs alleviate daunorubicin-induced cardiac microvascular injury via miR-186-5p/PARP9/STAT1 signal pathway.Regenerative therapy · 2024Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
aimsDoxorubicin (DOX)-induced heart failure has a poor prognosis, and effective treatments have not been established. Because DOX shows cumulative cardiotoxicity, we hypothesized that minimal cardiac remodelling occurred at the initial stage in activating cardiac fibroblasts. Our aim was to investigate the initial pathophysiology of DOX-exposed cardiac fibroblasts and propose prophylaxis. METHODS AND
resultsAn animal study was performed using a lower dose of DOX (4 mg/kg/week for 3 weeks, i.p.) than a toxic cumulative dose. Histological analysis was performed with terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling assay, picrosirius red staining, and immunohistochemical staining. The mechanism was analysed in vitro with a low dose of DOX, which did not induce cell apoptosis. Microarray analysis was performed. Differentially expressed genes were confirmed by enrichment analysis. Mitochondrial damage was assessed by mitochondrial membrane potential. The production of inflammatory cytokines and fibrosis markers was assessed by western blot, quantitative polymerase chain reaction, and ELISA. A phosphokinase antibody array was performed to detect related signalling pathways. Low-dose DOX did not induced cell death, and fibrosis was localized to the perivascular area in mice. Microarray analysis suggested that DOX induced genes associated with the innate immune system and inflammatory reactions, resulting in cardiac remodelling. DOX induced mitochondrial damage and increased the expression of interleukin-1. DOX also promoted the expression of fibrotic markers, such as alpha smooth muscle actin and galectin-3. These responses were induced through stress-activated protein kinase/c-Jun NH2-terminal kinase signalling. A peroxisome proliferator-activated receptor (PPARγ) agonist attenuated the expression of fibrotic markers through suppressing stress-activated protein kinase/c-Jun NH2-terminal kinase. Furthermore, this molecule also suppressed DOX-induced early fibrotic responses in vivo.
conclusionsLow-dose DOX provoked reactive fibrosis through sterile inflammation evoked by the damaged mitochondria.
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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.