ArticlePloS one2014
Notch-1 mediated cardiac protection following embryonic and induced pluripotent stem cell transplantation in doxorubicin-induced heart failure.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 2 of them syntheses that pooled it.
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Who cites it
25 citing papers in PubMed, 2 syntheses or guidelines pooled it, 39 citations in OpenAlex.
- Improving the preclinical models for the study of chemotherapy-induced cardiotoxicity: a Position Paper of the Italian Working Group on Drug Cardiotoxicity and Cardioprotection.Heart failure reviews · 2015Guideline
- Induced pluripotent stem cell therapies in heart failure treatment: a meta-analysis and systematic review.Regenerative medicinePooled it
- LncRNA GAS6-AS1 affects doxorubicin‑induced cardiomyocyte injury in H9c2 cells by regulating miR‑152‑3p: a cellular model relevant to heart failure.Journal of cardiothoracic surgery · 2026Article
- BMP-7 Treatment Ameliorates PTEN-Akt Mediated Apoptosis and Adverse Cardiac Remodeling in Ponatinib-Induced Cardiotoxicity.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Kuanxiong aerosol attenuates post-myocardial infarction heart failure by immune modulation via the NOTCH1 pathway.American journal of translational research · 2025Article
- Doxorubicin-induced apoptosis enhances monocyte infiltration and adverse cardiac remodeling in diabetic animals.Canadian journal of physiology and pharmacology · 2022Article
- Rat-Induced Pluripotent Stem Cells-Derived Cardiac Myocytes in a Cell Culture Dish.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Targeting Notch to Maximize Chemotherapeutic Benefits: Rationale, Advanced Strategies, and Future Perspectives.Cancers · 2021Review
- Article
- The Synergistic Effects ofDrug design, development and therapy · 2021Article
- Trophoblast Stem-Cell-Derived Exosomes Improve Doxorubicin-Induced Dilated Cardiomyopathy by Modulating the let-7i/YAP Pathway.Molecular therapy. Nucleic acids · 2020Article
- Article
- MiR322 mediates cardioprotection against ischemia/reperfusion injury via FBXW7/notch pathway.Journal of molecular and cellular cardiology · 2019Article
- Embryonic stem cell-derived exosomes inhibit doxorubicin-induced TLR4-NLRP3-mediated cell death-pyroptosis.American journal of physiology. Heart and circulatory physiology · 2019Article
- From Molecular Mechanisms to Clinical Management of Antineoplastic Drug-Induced Cardiovascular Toxicity: A Translational Overview.Antioxidants & redox signaling · 2019Review
- The Potential of Stem Cells and Stem Cell-Derived Exosomes in Treating Cardiovascular Diseases.Journal of cardiovascular translational research · 2019Review
- PTEN inhibitor VO-OHpic attenuates inflammatory M1 macrophages and cardiac remodeling in doxorubicin-induced cardiomyopathy.American journal of physiology. Heart and circulatory physiology · 2018Article
- Review
- Embryonic stem cell-derived cardiomyocytes for the treatment of doxorubicin-induced cardiomyopathy.Stem cell research & therapy · 2018Article
- Automated Segmentation of Light-Sheet Fluorescent Imaging to Characterize Experimental Doxorubicin-Induced Cardiac Injury and Repair.Scientific reports · 2017Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Doxorubicin (DOX), an effective chemotherapeutic drug used in the treatment of various cancers, is limited in its clinical applications due to cardiotoxicity. Recent studies suggest that transplanted adult stem cells inhibit DOX-induced cardiotoxicity. However, the effects of transplanted embryonic stem (ES) and induced pluripotent stem (iPS) cells are completely unknown in DOX-induced left ventricular dysfunction following myocardial infarction (MI). In brief, C57BL/6 mice were divided into five groups: Sham, DOX-MI, DOX-MI+cell culture (CC) media, DOX-MI+ES cells, and DOX-MI+iPS cells. Mice were injected with cumulative dose of 12 mg/kg of DOX and 2 weeks later, MI was induced by coronary artery ligation. Following ligation, 5×10(4) ES or iPS cells were delivered into the peri-infarct region. At day 14 post-MI, echocardiography was performed, mice were sacrificed, and hearts were harvested for further analyses. Our data reveal apoptosis was significantly inhibited in ES and iPS cell transplanted hearts compared with respective controls (DOX-MI+ES: 0.48±0.06% and DOX-MI+iPS: 0.33±0.05% vs. DOX-MI: 1.04±0.07% and DOX-MI+CC: 0.96±0.21%; p<0.05). Furthermore, a significant increase in levels of Notch-1 (p<0.05), Hes1 (p<0.05), and pAkt (p<0.05) were observed whereas a decrease in the levels of PTEN (p<0.05), a negative regulator of Akt, was evident following stem cell transplantation. Moreover, hearts transplanted with stem cells demonstrated decreased vascular and interstitial fibrosis (p<0.05) as well as MMP-9 expression (p<0.01) compared with controls. Additionally, heart function was significantly improved (p<0.05) in both cell-transplanted groups. In conclusion, our data show that transplantation of ES and iPS cells blunt DOX-induced adverse cardiac remodeling, which is associated with improved cardiac function, and these effects are mediated by the Notch pathway.
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