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http://hdl.handle.net/10662/20250
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Campo DC | Valor | idioma |
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dc.contributor.author | Fattah, Caroline | - |
dc.contributor.author | Nather, Katrin | - |
dc.contributor.author | McCarroll, Charlotte S. | - |
dc.contributor.author | Hortigón Vinagre, Maria Pura | - |
dc.contributor.author | Zamora Rodríguez, Víctor | - |
dc.contributor.author | Flores Muñoz, Mónica | - |
dc.contributor.author | McArthur, Lisa | - |
dc.contributor.author | Zentilin, Lorena | - |
dc.contributor.author | Giacca, Mauro | - |
dc.contributor.author | Touyz, Rhian M. | - |
dc.contributor.author | Smith, Godfrey L. | - |
dc.contributor.author | Loughrey, Christopher M. | - |
dc.contributor.author | Nicklin, Stuart A. | - |
dc.date.accessioned | 2024-02-07T11:10:13Z | - |
dc.date.available | 2024-02-07T11:10:13Z | - |
dc.date.issued | 2016 | - |
dc.identifier.issn | 0735-1097 | - |
dc.identifier.uri | http://hdl.handle.net/10662/20250 | - |
dc.description.abstract | Background Angiotensin-(1-9) [Ang-(1-9)] is a novel peptide of the counter-regulatory axis of the renin-angiotensin-aldosterone system previously demonstrated to have therapeutic potential in hypertensive cardiomyopathy when administered via osmotic mini-pump. Here, we investigate whether gene transfer of Ang-(1-9) is cardioprotective in a murine model of myocardial infarction (MI). Objectives The authors evaluated effects of Ang-(1-9) gene therapy on myocardial structural and functional remodeling post-infarction. Methods C57BL/6 mice underwent permanent left anterior descending coronary artery ligation and cardiac function was assessed using echocardiography for 8 weeks followed by a terminal measurement of left ventricular pressure volume loops. Ang-(1-9) was delivered by adeno-associated viral vector via single tail vein injection immediately following induction of MI. Direct effects of Ang-(1-9) on cardiomyocyte excitation/contraction coupling and cardiac contraction were evaluated in isolated mouse and human cardiomyocytes and in an ex vivo Langendorff-perfused whole-heart model. Results Gene delivery of Ang-(1-9) reduced sudden cardiac death post-MI. Pressure volume measurements revealed complete restoration of end-systolic pressure, ejection fraction, end-systolic volume, and the end-diastolic pressure volume relationship by Ang-(1-9) treatment. Stroke volume and cardiac output were significantly increased versus sham. Histological analysis revealed only mild effects on cardiac hypertrophy and fibrosis, but a significant increase in scar thickness. Direct assessment of Ang-(1-9) on isolated cardiomyocytes demonstrated a positive inotropic effect via increasing calcium transient amplitude and contractility. Ang-(1-9) increased contraction in the Langendorff model through a protein kinase A–dependent mechanism. Conclusions Our novel findings showed that Ang-(1-9) gene therapy preserved left ventricular systolic function post-MI, restoring cardiac function. Furthermore, Ang-(1-9) directly affected cardiomyocyte calcium handling through a protein kinase A–dependent mechanism. These data emphasized Ang-(1-9) gene therapy as a potential new strategy in the context of MI | es_ES |
dc.description.sponsorship | This work was supported by a British Heart Foundation PhD Studentship (FS/09/052/28032), BHF project grant (PG/11/43/28901), and an MRC Confidence in Concept Award (MC_PC_13063), and MRC Research Grant (G0901161). Dr. Zamora is recipient of a postdoctoral fellowship from Fundacion Alfonso Martin Escudero, Spain. | - |
dc.format.extent | 15 p. | es_ES |
dc.format.mimetype | application/pdf | en_US |
dc.language.iso | eng | es_ES |
dc.publisher | Elsevier | es_ES |
dc.rights | Atribución 4.0 Internacional | * |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | * |
dc.subject | Adeno-associated virus | es_ES |
dc.subject | Calcium | es_ES |
dc.subject | Inotropy | es_ES |
dc.subject | Renin angiotensin system | es_ES |
dc.subject | Virus adenoasociado | - |
dc.subject | Calcio | - |
dc.subject | Inotropía | - |
dc.subject | Sistema renina angiotensina | - |
dc.title | Gene therapy with angiotensin-(1-9) preserves left ventricular systolic function after myocardial infarction | es_ES |
dc.type | article | es_ES |
dc.description.version | peerReviewed | es_ES |
europeana.type | TEXT | en_US |
dc.rights.accessRights | openAccess | es_ES |
dc.subject.unesco | 3205.01Cardiología | - |
europeana.dataProvider | Universidad de Extremadura. España | es_ES |
dc.identifier.bibliographicCitation | Fattah, C., Nather, K., McCarroll, C. S., Hortigon-Vinagre, M. P., Zamora, V., Flores-Munoz, M., McArthur, L., Zentilin, L., Giacca, M., Touyz, R. M., Smith, G. L., Loughrey, C. M., & Nicklin, S. A. (2016). Gene Therapy With Angiotensin-(1-9) Preserves Left Ventricular Systolic Function After Myocardial Infarction. Journal of the American College of Cardiology, 68(24), 2652-2666. https://doi.org/10.1016/j.jacc.2016.09.946 | es_ES |
dc.type.version | publishedVersion | es_ES |
dc.contributor.affiliation | Universidad de Extremadura. Departamento de Bioquímica, Biología Molecular y Genética | es_ES |
dc.contributor.affiliation | University of Glasgow. UK | - |
dc.contributor.affiliation | Universidad Veracruzana. México | - |
dc.relation.publisherversion | https://www.sciencedirect.com/science/article/pii/S0735109716365755 | - |
dc.identifier.doi | 10.1016/j.jacc.2016.09.946 | - |
dc.identifier.publicationtitle | Journal of the American College of Cardiology | es_ES |
dc.identifier.publicationfirstpage | 2652 | es_ES |
dc.identifier.publicationlastpage | 2666 | es_ES |
dc.identifier.publicationvolume | 68 (24) | es_ES |
dc.identifier.orcid | 0000-0001-5531-1779 | es_ES |
dc.identifier.orcid | 0000-0003-0102-2677 | - |
Colección: | DBYBM - Artículos |
Archivos
Archivo | Descripción | Tamaño | Formato | |
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j_jacc_2016_09_946.pdf | 3,11 MB | Adobe PDF | Descargar |
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