ArticleHeart, lung & circulation2019
Doxorubicin-Induced Myocardial Fibrosis Involves the Neurokinin-1 Receptor and Direct Effects on Cardiac Fibroblasts.
Article in Heart, lung & circulation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 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
45 citing papers in PubMed, 2 syntheses or guidelines pooled it, 77 citations in OpenAlex.
- A narrative review of metabolomics approaches in identifying biomarkers of doxorubicin-induced cardiotoxicity.Metabolomics : Official journal of the Metabolomic Society · 2025Pooled 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
- Neuregulin-1β Mitigates Doxorubicin-Induced Cardiotoxicity viaInternational journal of molecular sciences · 2026Article
- The Role of Gut Microbiota and Their Derived Metabolites in Chemotherapy-Induced Nausea and Vomiting in Ovarian Cancer.Cancer medicine · 2026Article
- Exposure of endothelial cells to doxorubicin inhibits extracellular matrix production by dermal fibroblasts in a paracrine manner.Toxicological sciences : an official journal of the Society of Toxicology · 2026Article
- Canadine protects against doxorubicin-induced cardiac and brain injury by inhibiting Oxidative stress.BMC pharmacology & toxicology · 2026Article
- Lycorine Attenuates Cardiac Fibrosis Through the Regulation of PYK2 Expression and Activity.Cardiovascular therapeutics · 2026Article
- Integration of cAMP and TRPV4 Signaling to Optimize Collagen Remodeling for Management of Fibrosis.Cells · 2025Review
- Nanomedicine-Based Strategies for Mitigating Chemo/Radiotherapy-Induced Cardiac Inflammation and Fibrosis.Cardiovascular toxicology · 2025Review
- The role of nitric oxide and connexin 43 in the cardioprotective effects of apigenin against doxorubicin-induced cardiotoxicity in male rats.Molecular biology reports · 2025Article
- Drug Repositioning in Doxorubicin-Induced Cardiotoxicity Protection.International journal of molecular sciences · 2025Review
- Temporal Dynamics of Extracellular Matrix Remodeling in Anthracycline-Induced Cardiotoxicity.Cells · 2025Review
- The orphan nuclear receptor Nr4a1 contributes to interstitial cardiac fibrosis via modulation of cardiac fibroblast and macrophage phenotype.Cellular and molecular life sciences : CMLS · 2024Article
- Cellular metabolism of substance P produces neurokinin-1 receptor peptide agonists with diminished cyclic AMP signaling.American journal of physiology. Cell physiology · 2024Article
- Two-dimensional Speckle Tracking Imaging in Cardiotoxicity Caused by Treatment of Breast Carcinoma with Anthracyclines.Journal of Cancer · 2024Article
- Anticancer drugs and cardiotoxicity: the role of cardiomyocyte and non-cardiomyocyte cells.Frontiers in cardiovascular medicine · 2024Review
- Sibjotang Protects against Cardiac Hypertrophy In Vitro and In Vivo.Life (Basel, Switzerland) · 2023Article
- The immunology of heart failure with preserved ejection fraction.Clinical science (London, England : 1979) · 2023Review
- New Insight Into Cardioprotection From Anthracyclines: Still Converging on the Mitochondria.JACC. CardioOncology · 2023Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundCancer patients receiving anthracycline-based chemotherapy (Anth-bC) may experience early cardiac fibrosis, which could be an important contributing mechanism to the development of impaired left ventricular (LV) function. Substance P, a neuropeptide that predominantly acts via the neurokinin 1 receptor (NK-1R), contributes to adverse myocardial remodelling and fibrosis in other cardiomyopathies. We sought to determine if NK-1R blockade is effective against doxorubicin (Dox - a frequently used Anth-bC)-induced cardiac fibrosis and cardiomyocyte apoptosis. In addition, we explored the direct effects of Dox on cardiac fibroblasts.
methodsMale Sprague-Dawley rats were randomised to receive saline, six cycles of Dox (1.5mg Dox/kg/cycle) or Dox with an NK-1R antagonist (L732138, 5mg/kg/daily through Dox treatment). At 8 weeks after the initial dose of Dox, LV function and histopathological myocardial fibrosis and cell apoptosis were assessed. Collagen secretion was measured in vitro to test direct Dox activation of cardiac fibroblasts.
resultsRats undergoing Dox treatment (9mg/kg cumulative dose) developed cardiac fibrosis and cardiomyocyte apoptosis. NK-1R blockade partially mitigated cardiac fibrosis while completely preventing cardiomyocyte apoptosis. This resulted in improved diastolic function. Furthermore, we found that Dox had direct effects on cardiac fibroblasts to cause increased collagen production and enhanced cell survival.
conclusionsThis study demonstrates that cardiac fibrosis induced by Anth-bC can be reduced by NK-1R blockade. The residual fibrotic response is likely due to direct Dox effects on cardiac fibroblasts to produce collagen.
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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.