دورية أكاديمية
Recombinant human soluble domain of CD39L3 and ticagrelor: cardioprotective effects in experimental myocardial infarction.
| العنوان: | Recombinant human soluble domain of CD39L3 and ticagrelor: cardioprotective effects in experimental myocardial infarction. |
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| المؤلفون: | Vilahur G; Research Institute, Hospital de la Santa Creu i Sant Pau, IIB-Sant Pau, C/Sant Antoni Mª Claret 167, Barcelona 08025, Spain.; Centro de Investigación Biomédica en Red Cardiovascular (CIBERCV), Instituto de Salud Carlos III, Madrid, Spain., Radike M; Research Institute, Hospital de la Santa Creu i Sant Pau, IIB-Sant Pau, C/Sant Antoni Mª Claret 167, Barcelona 08025, Spain.; Radiology Department, Liverpool Heart and Chest Hospital NHS Foundation Trust, Liverpool, UK., Sutelman P; Research Institute, Hospital de la Santa Creu i Sant Pau, IIB-Sant Pau, C/Sant Antoni Mª Claret 167, Barcelona 08025, Spain., Ben-Aicha S; Research Institute, Hospital de la Santa Creu i Sant Pau, IIB-Sant Pau, C/Sant Antoni Mª Claret 167, Barcelona 08025, Spain., Gutiérrez M; Research Institute, Hospital de la Santa Creu i Sant Pau, IIB-Sant Pau, C/Sant Antoni Mª Claret 167, Barcelona 08025, Spain., Casaní L; Research Institute, Hospital de la Santa Creu i Sant Pau, IIB-Sant Pau, C/Sant Antoni Mª Claret 167, Barcelona 08025, Spain., Hovdal D; DMPK, Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden., Ongstad EL; Bioscience Cardiovascular, Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA., Gabrielsen A; Early Clinical Development, Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden., Hidalgo A; Radiology Department, Hospital Josep Trueta, Girona, Spain., Fjellström O; Projects, Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden., Carlsson L; Bioscience Cardiovascular, Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA., Badimon L; Research Institute, Hospital de la Santa Creu i Sant Pau, IIB-Sant Pau, C/Sant Antoni Mª Claret 167, Barcelona 08025, Spain.; Centro de Investigación Biomédica en Red Cardiovascular (CIBERCV), Instituto de Salud Carlos III, Madrid, Spain. |
| المصدر: | European heart journal [Eur Heart J] 2024 May 07; Vol. 45 (17), pp. 1553-1567. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Oxford University Press Country of Publication: England NLM ID: 8006263 Publication Model: Print Cited Medium: Internet ISSN: 1522-9645 (Electronic) Linking ISSN: 0195668X NLM ISO Abbreviation: Eur Heart J Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2005- : Oxford : Oxford University Press Original Publication: London, Saunders [etc.] |
| مواضيع طبية MeSH: | Apyrase*/metabolism , Myocardial Infarction*/drug therapy , Ticagrelor*/pharmacology , Ticagrelor*/therapeutic use , Adenosine Triphosphatases*/pharmacology , Adenosine Triphosphatases*/therapeutic use, Animals ; Humans ; Male ; Adenosine/analogs & derivatives ; Adenosine/pharmacology ; Antigens, CD ; Cardiotonic Agents/pharmacology ; Cardiotonic Agents/therapeutic use ; Disease Models, Animal ; Platelet Aggregation/drug effects ; Recombinant Proteins/pharmacology ; Recombinant Proteins/therapeutic use ; Swine |
| مستخلص: | Background and Aims: The ecto-nucleoside triphosphate diphosphohydrolases of the CD39 family degrade ATP and ADP into AMP, which is converted into adenosine by the extracellular CD73/ecto-5-nucleotidase. This pathway has been explored in antithrombotic treatments but little in myocardial protection. We have investigated whether the administration of solCD39L3 (AZD3366) confers additional cardioprotection to that of ticagrelor alone in a pre-clinical model of myocardial infarction (MI). Methods: Ticagrelor-treated pigs underwent balloon-induced MI (90 min) and, before reperfusion, received intravenously either vehicle, 1 mg/kg AZD3366 or 3 mg/kg AZD3366. All animals received ticagrelor twice daily for 42 days. A non-treated MI group was run as a control. Serial cardiac magnetic resonance (baseline, Day 3 and Day 42 post-MI), light transmittance aggregometry, bleeding time, and histological and molecular analyses were performed. Results: Ticagrelor reduced oedema formation and infarct size at Day 3 post-MI vs. controls. A 3 mg/kg AZD3366 provided an additional 45% reduction in oedema and infarct size compared with ticagrelor and a 70% reduction vs. controls (P < .05). At Day 42, infarct size declined in all ticagrelor-administered pigs, particularly in 3 mg/kg AZD3366-treated pigs (P < .05). Left ventricular ejection fraction was diminished at Day 3 in placebo pigs and worsened at Day 42, whereas it remained unaltered in ticagrelor ± AZD3366-administered animals. Pigs administered with 3 mg/kg AZD3366 displayed higher left ventricular ejection fraction upon dobutamine stress at Day 3 and minimal dysfunctional segmental contraction at Day 42 (χ2P < .05 vs. all). Cardiac and systemic molecular readouts supported these benefits. Interestingly, AZD3366 abolished ADP-induced light transmittance aggregometry without affecting bleeding time. Conclusions: Infusion of AZD3366 on top of ticagrelor leads to enhanced cardioprotection compared with ticagrelor alone. (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.) |
| معلومات مُعتمدة: | PID2021-128891OB-I00 AstraZeneca; MCIN/AEI/10.13039/501100011033 NextGenerationEU; Fondo Europeo de Desarrollo Regional; CB16/11/00411 Instituto de Salud Carlos III; 2017SGR1480 Generalitat of Catalunya-Secretaria d'Universitats i Recerca del Departament d'Economia i Coneixement de la Generalitat; Generalitat de Cataluña, and Fundación Investigación Cardiovascular; Fundación Jesús Serra |
| فهرسة مساهمة: | Keywords: Adenosine; CMR imaging; Cardioprotection; Pigs; Soluble CD39L3; Ticagrelor |
| المشرفين على المادة: | K72T3FS567 (Adenosine) 0 (Antigens, CD) EC 3.6.1.5 (Apyrase) 0 (Cardiotonic Agents) EC 3.6.1.5 (CD39 antigen) 0 (Recombinant Proteins) GLH0314RVC (Ticagrelor) EC 3.6.1.- (ectoATPase) EC 3.6.1.- (Adenosine Triphosphatases) |
| تواريخ الأحداث: | Date Created: 20240315 Date Completed: 20240507 Latest Revision: 20240603 |
| رمز التحديث: | 20240604 |
| DOI: | 10.1093/eurheartj/ehae107 |
| PMID: | 38486376 |
| قاعدة البيانات: | MEDLINE |
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