دورية أكاديمية
Remote ischaemic preconditioning ameliorates anthracycline-induced cardiotoxicity and preserves mitochondrial integrity.
| العنوان: | Remote ischaemic preconditioning ameliorates anthracycline-induced cardiotoxicity and preserves mitochondrial integrity. |
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| المؤلفون: | Galán-Arriola C; Translational Laboratory for Cardiovascular Imaging and Therapy, Centro Nacional de Investigaciones Cardiovasculares (CNIC), c/Melchor Fernandez Almagro, 3. 28029 Madrid, Spain.; Centro de Investigación Biomédica en Red en Enfermedades Cardiovasculares (CIBERCV), Spain., Villena-Gutiérrez R; Translational Laboratory for Cardiovascular Imaging and Therapy, Centro Nacional de Investigaciones Cardiovasculares (CNIC), c/Melchor Fernandez Almagro, 3. 28029 Madrid, Spain.; Centro de Investigación Biomédica en Red en Enfermedades Cardiovasculares (CIBERCV), Spain., Higuero-Verdejo MI; Translational Laboratory for Cardiovascular Imaging and Therapy, Centro Nacional de Investigaciones Cardiovasculares (CNIC), c/Melchor Fernandez Almagro, 3. 28029 Madrid, Spain., Díaz-Rengifo IA; Translational Laboratory for Cardiovascular Imaging and Therapy, Centro Nacional de Investigaciones Cardiovasculares (CNIC), c/Melchor Fernandez Almagro, 3. 28029 Madrid, Spain., Pizarro G; Translational Laboratory for Cardiovascular Imaging and Therapy, Centro Nacional de Investigaciones Cardiovasculares (CNIC), c/Melchor Fernandez Almagro, 3. 28029 Madrid, Spain.; Centro de Investigación Biomédica en Red en Enfermedades Cardiovasculares (CIBERCV), Spain.; Complejo Hospitalario Ruber Juan Bravo, Madrid, Spain., López GJ; Translational Laboratory for Cardiovascular Imaging and Therapy, Centro Nacional de Investigaciones Cardiovasculares (CNIC), c/Melchor Fernandez Almagro, 3. 28029 Madrid, Spain., Molina-Iracheta A; Translational Laboratory for Cardiovascular Imaging and Therapy, Centro Nacional de Investigaciones Cardiovasculares (CNIC), c/Melchor Fernandez Almagro, 3. 28029 Madrid, Spain., Pérez-Martínez C; Facultad de Veterinaria de León, León, Spain., García RD; Translational Laboratory for Cardiovascular Imaging and Therapy, Centro Nacional de Investigaciones Cardiovasculares (CNIC), c/Melchor Fernandez Almagro, 3. 28029 Madrid, Spain., González-Calle D; Translational Laboratory for Cardiovascular Imaging and Therapy, Centro Nacional de Investigaciones Cardiovasculares (CNIC), c/Melchor Fernandez Almagro, 3. 28029 Madrid, Spain.; Centro de Investigación Biomédica en Red en Enfermedades Cardiovasculares (CIBERCV), Spain.; Department of Cardiology, Hospital Universitario Salamanca-IBSAL, Salamanca, Spain., Lobo M; Translational Laboratory for Cardiovascular Imaging and Therapy, Centro Nacional de Investigaciones Cardiovasculares (CNIC), c/Melchor Fernandez Almagro, 3. 28029 Madrid, Spain.; Centro de Investigación Biomédica en Red en Enfermedades Cardiovasculares (CIBERCV), Spain.; Department of Cardiology, IIS-Fundación Jiménez Díaz Hospital, Madrid, Spain., Sánchez PL; Centro de Investigación Biomédica en Red en Enfermedades Cardiovasculares (CIBERCV), Spain.; Department of Cardiology, Hospital Universitario Salamanca-IBSAL, Salamanca, Spain., Oliver E; Translational Laboratory for Cardiovascular Imaging and Therapy, Centro Nacional de Investigaciones Cardiovasculares (CNIC), c/Melchor Fernandez Almagro, 3. 28029 Madrid, Spain.; Centro de Investigación Biomédica en Red en Enfermedades Cardiovasculares (CIBERCV), Spain., Córdoba R; Department of Cardiology, IIS-Fundación Jiménez Díaz Hospital, Madrid, Spain., Fuster V; Translational Laboratory for Cardiovascular Imaging and Therapy, Centro Nacional de Investigaciones Cardiovasculares (CNIC), c/Melchor Fernandez Almagro, 3. 28029 Madrid, Spain.; The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, USA., Sánchez-González J; Philips Healthcare, Madrid, Spain., Ibanez B; Translational Laboratory for Cardiovascular Imaging and Therapy, Centro Nacional de Investigaciones Cardiovasculares (CNIC), c/Melchor Fernandez Almagro, 3. 28029 Madrid, Spain.; Centro de Investigación Biomédica en Red en Enfermedades Cardiovasculares (CIBERCV), Spain.; Department of Cardiology, IIS-Fundación Jiménez Díaz Hospital, Madrid, Spain. |
| المصدر: | Cardiovascular research [Cardiovasc Res] 2021 Mar 21; Vol. 117 (4), pp. 1132-1143. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Oxford Journals Country of Publication: England NLM ID: 0077427 Publication Model: Print Cited Medium: Internet ISSN: 1755-3245 (Electronic) Linking ISSN: 00086363 NLM ISO Abbreviation: Cardiovasc Res Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2008- : Oxford : Oxford Journals Original Publication: London, British Medical Assn. |
| مواضيع طبية MeSH: | Ischemic Preconditioning* , Stroke Volume* , Ventricular Function, Left* , Ventricular Remodeling*, Heart Diseases/*prevention & control , Hindlimb/*blood supply , Mitochondria, Heart/*ultrastructure , Myocardium/*ultrastructure, Animals ; Antibiotics, Antineoplastic ; Autophagy ; Autophagy-Related Proteins/metabolism ; Cardiotoxicity ; Disease Models, Animal ; Doxorubicin ; Fibrosis ; Heart Diseases/chemically induced ; Heart Diseases/pathology ; Heart Diseases/physiopathology ; Magnetic Resonance Imaging, Cine ; Male ; Mitochondria, Heart/metabolism ; Mitochondrial Dynamics ; Myocardium/metabolism ; Regional Blood Flow ; Sus scrofa ; Time Factors |
| مستخلص: | Aims: Anthracycline-induced cardiotoxicity (AIC) is a serious adverse effect among cancer patients. A central mechanism of AIC is irreversible mitochondrial damage. Despite major efforts, there are currently no effective therapies able to prevent AIC. Methods and Results: Forty Large-White pigs were included. In Study 1, 20 pigs were randomized 1:1 to remote ischaemic preconditioning (RIPC, 3 cycles of 5 min leg ischaemia followed by 5 min reperfusion) or no pretreatment. RIPC was performed immediately before each intracoronary doxorubicin injections (0.45 mg/kg) given at Weeks 0, 2, 4, 6, and 8. A group of 10 pigs with no exposure to doxorubicin served as healthy controls. Pigs underwent serial cardiac magnetic resonance (CMR) exams at baseline and at Weeks 6, 8, 12, and 16, being sacrifice after that. In Study 2, 10 new pigs received 3 doxorubicin injections (with/out preceding RIPC) and were sacrificed at week 6. In Study 1, left ventricular ejection fraction (LVEF) depression was blunted animals receiving RIPC before doxorubicin (RIPC-Doxo), which had a significantly higher LVEF at Week 16 than doxorubicin treated pigs that received no pretreatment (Untreated-Doxo) (41.5 ± 9.1% vs. 32.5 ± 8.7%, P = 0.04). It was mainly due to conserved regional contractile function. In Study 2, transmission electron microscopy (TEM) at Week 6 showed fragmented mitochondria with severe morphological abnormalities in Untreated-Doxo pigs, together with upregulation of fission and autophagy proteins. At the end of the 16-week Study 1 protocol, TEM revealed overt mitochondrial fragmentation with structural fragmentation in Untreated-Doxo pigs, whereas interstitial fibrosis was less severe in RIPC+Doxo pigs. Conclusion: In a translatable large-animal model of AIC, RIPC applied immediately before each doxorubicin injection resulted in preserved cardiac contractility with significantly higher long-term LVEF and less cardiac fibrosis. RIPC prevented mitochondrial fragmentation and dysregulated autophagy from AIC early stages. RIPC is a promising intervention for testing in clinical trials in AIC. (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.) |
| التعليقات: | Comment in: Cardiovasc Res. 2021 Mar 21;117(4):985-986. (PMID: 32637985) |
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| فهرسة مساهمة: | Keywords: Anthracyclines; Cardio-oncology; Cardiotoxicity; Magnetic resonance imaging; Mitochondria; Remote conditioning |
| المشرفين على المادة: | 0 (Antibiotics, Antineoplastic) 0 (Autophagy-Related Proteins) 80168379AG (Doxorubicin) |
| تواريخ الأحداث: | Date Created: 20200630 Date Completed: 20220104 Latest Revision: 20240331 |
| رمز التحديث: | 20240331 |
| مُعرف محوري في PubMed: | PMC7983009 |
| DOI: | 10.1093/cvr/cvaa181 |
| PMID: | 32597960 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1755-3245 |
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| DOI: | 10.1093/cvr/cvaa181 |