ArticlePloS one2011
Cardiomyocyte specific ablation of p53 is not sufficient to block doxorubicin induced cardiac fibrosis and associated cytoskeletal changes.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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.
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Who cites it
20 citing papers in PubMed, 57 citations in OpenAlex.
- Cardiomyopathies and a brief insight into DOX-induced cardiomyopathy.The Egyptian heart journal : (EHJ) : official bulletin of the Egyptian Society of Cardiology · 2025Review
- Anthracycline-induced cardiotoxicity and cell senescence: new therapeutic option?Cellular and molecular life sciences : CMLS · 2022Review
- Therapeutic Targets for DOX-Induced Cardiomyopathy: Role of Apoptosis vs. Ferroptosis.International journal of molecular sciences · 2022Review
- Regulation of Transplanted Cell Homing by FGF1 and PDGFB after Doxorubicin Myocardial Injury.Cells · 2021Article
- Cardiotoxicity of Cancer Treatments: Focus on Anthracycline Cardiomyopathy.Arteriosclerosis, thrombosis, and vascular biology · 2021Review
- Plasma microrna expression profile for reduced ejection fraction in dilated cardiomyopathy.Scientific reports · 2021Article
- Article
- Review
- Effects of β-adrenergic receptor drugs on embryonic ventricular cell proliferation and differentiation and their impact on donor cell transplantation.American journal of physiology. Heart and circulatory physiology · 2017Article
- Ataxia telangiectasia mutated in cardiac fibroblasts regulates doxorubicin-induced cardiotoxicity.Cardiovascular research · 2016Article
- Epigenetic factors MeCP2 and HDAC6 control α-tubulin acetylation in cardiac fibroblast proliferation and fibrosis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2016Article
- Endogenous nitric oxide regulates blood vessel growth factors, capillaries in the cortex, and memory retention in Sprague-Dawley rats.American journal of translational research · 2016Article
- Impaired sinoatrial node function and increased susceptibility to atrial fibrillation in mice lacking natriuretic peptide receptor C.The Journal of physiology · 2015Article
- Endothelial p53 deletion improves angiogenesis and prevents cardiac fibrosis and heart failure induced by pressure overload in mice.Journal of the American Heart Association · 2015Article
- Nanocurcumin Prevents Hypoxia Induced Stress in Primary Human Ventricular Cardiomyocytes by Maintaining Mitochondrial Homeostasis.PloS one · 2015Article
- The tell-tale heart: molecular and cellular responses to childhood anthracycline exposure.American journal of physiology. Heart and circulatory physiology · 2014Review
- Quercetin attenuates doxorubicin cardiotoxicity by modulating Bmi-1 expression.British journal of pharmacology · 2014Article
- Sulforaphane induces oxidative stress and death by p53-independent mechanism: implication of impaired glutathione recycling.PloS one · 2014Article
- A novel insight into the cardiotoxicity of antineoplastic drug doxorubicin.International journal of molecular sciences · 2013Article
- Cardiac side effects of anticancer treatments: new mechanistic insights.Current heart failure reports · 2012Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Doxorubicin (Dox) is an anthracycline used to effectively treat several forms of cancer. Unfortunately, the use of Dox is limited due to its association with cardiovascular complications which are manifested as acute and chronic cardiotoxicity. The pathophysiological mechanism of Dox induced cardiotoxicity appears to involve increased expression of the tumor suppressor protein p53 in cardiomyocytes, followed by cellular apoptosis. It is not known whether downregulation of p53 expression in cardiomyocytes would result in decreased rates of myocardial fibrosis which occurs in response to cardiomyocyte loss. Further, it is not known whether Dox can induce perivascular necrosis and associated fibrosis in the heart. In this study we measured the effects of acute Dox treatment on myocardial and perivascular apoptosis and fibrosis in a conditional knockout (CKO) mouse model system which harbours inactive p53 alleles specifically in cardiomyocytes. CKO mice treated with a single dose of Dox (20 mg/kg), did not display lower levels of myocardial apoptosis or reactive oxygen and nitrogen species (ROS/RNS) compared to control mice with intact p53 alleles. Interestingly, CKO mice also displayed higher levels of interstitial and perivascular fibrosis compared to controls 3 or 7 days after Dox treatment. Additionally, the decrease in levels of the microtubule protein α-tubulin, which occurs in response to Dox treatment, was not prevented in CKO mice. Overall, these results indicate that selective loss of p53 in cardiomyocytes is not sufficient to prevent Dox induced myocardial ROS/RNS generation, apoptosis, interstitial fibrosis and perivascular fibrosis. Further, these results support a role for p53 independent apoptotic pathways leading to Dox induced myocardial damage and highlight the importance of vascular lesions in Dox induced cardiotoxicity.
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Registered trials
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