MicroRNAs have been associated with cardiomyocyte apoptosis, a process involved in myocardial remodelling in aortic valve (Av) stenosis (AS). Our aim was to analyse whether the dysregulation of myocardial microRNAs was related to cardiomyocyte apoptosis in AS patients. Endomyocardial biopsies were obtained from 28 patients with severe AS (based on pressure gradients and Av area) referred for Av replacement and from necropsies of 10 cardiovascular disease-free control subjects. AS patients showed an increased (P<0.001) cardiomyocyte apoptotic index (CMAI) compared with controls. Two clusters of patients were identified according to the CMAI: group 1 (CMAI ≤ 0.08%; n=16) and group 2 (CMAI > 0.08%; n=12). Group 2 patients presented lower cardiomyocyte density (P<0.001) and ejection fraction (P<0.05), and higher troponin T levels (P<0.05), prevalence of heart failure (HF; P<0.05) and NT-proBNP levels (P<0.05) than those from group 1. miRNA expression profile analysed in 5 patients randomly selected from each group showed 64 microRNAs down-regulated and 6 up-regulated (P<0.05) in group 2 compared with group 1. Those microRNAs with the highest fold-change were validated in the full two groups corroborating that miR-10b, miR-125b-2* and miR-338-3p were down-regulated (P<0.05) in group 2 compared with group 1 and control subjects. These three microRNAs were inversely correlated (P<0.05) with the CMAI. Inhibition of miR-10b induced an increase (P<0.05) of apoptosis and increased expression (P<0.05) of apoptosis protease-activating factor-1 (Apaf-1) in HL-1 cardiomyocytes. In conclusion, myocardial down-regulation of miR-10b may be involved in increased cardiomyocyte apoptosis in AS patients, probably through Apaf-1 up-regulation, contributing to cardiomyocyte damage and to the development of HF.
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IL-13 induced actin cytoskeleton rearrangement in human podocytes. Magnification, x60, scale bar, 20μm. For more information please see pp. 2317-2327. Image provided by Chan Chang Yien.
Research Article|
October 20 2016
Potential role of microRNA-10b down-regulation in cardiomyocyte apoptosis in aortic stenosis patients
Idoia Gallego;
Idoia Gallego
1
*Program of Cardiovascular Diseases, Centre for Applied Medical Research, University of Navarra, Pamplona 31008, Spain
†IdiSNA, Navarra Institute for Health Research, Pamplona 31008, Spain
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Javier Beaumont;
Javier Beaumont
1
*Program of Cardiovascular Diseases, Centre for Applied Medical Research, University of Navarra, Pamplona 31008, Spain
†IdiSNA, Navarra Institute for Health Research, Pamplona 31008, Spain
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Begoña López;
Begoña López
*Program of Cardiovascular Diseases, Centre for Applied Medical Research, University of Navarra, Pamplona 31008, Spain
†IdiSNA, Navarra Institute for Health Research, Pamplona 31008, Spain
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Susana Ravassa;
Susana Ravassa
*Program of Cardiovascular Diseases, Centre for Applied Medical Research, University of Navarra, Pamplona 31008, Spain
†IdiSNA, Navarra Institute for Health Research, Pamplona 31008, Spain
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Juan José Gómez-Doblas;
Juan José Gómez-Doblas
‡Division of Cardiology, Virgen de la Victoria University Hospital, Málaga 29010, Spain
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María Ujué Moreno;
María Ujué Moreno
*Program of Cardiovascular Diseases, Centre for Applied Medical Research, University of Navarra, Pamplona 31008, Spain
†IdiSNA, Navarra Institute for Health Research, Pamplona 31008, Spain
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Félix Valencia;
Félix Valencia
‡Division of Cardiology, Virgen de la Victoria University Hospital, Málaga 29010, Spain
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Eduardo de Teresa;
Eduardo de Teresa
‡Division of Cardiology, Virgen de la Victoria University Hospital, Málaga 29010, Spain
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Javier Díez;
*Program of Cardiovascular Diseases, Centre for Applied Medical Research, University of Navarra, Pamplona 31008, Spain
†IdiSNA, Navarra Institute for Health Research, Pamplona 31008, Spain
§Department of Cardiology and Cardiac Surgery, University Clinic, University of Navarra, Pamplona 31008, Spain
Correspondence: Arantxa González (email [email protected]) or Javier Díez (email [email protected]).
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Arantxa González
*Program of Cardiovascular Diseases, Centre for Applied Medical Research, University of Navarra, Pamplona 31008, Spain
†IdiSNA, Navarra Institute for Health Research, Pamplona 31008, Spain
Correspondence: Arantxa González (email [email protected]) or Javier Díez (email [email protected]).
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Publisher: Portland Press Ltd
Received:
June 21 2016
Revision Received:
August 26 2016
Accepted:
September 12 2016
Accepted Manuscript online:
September 13 2016
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society
2016
Clin Sci (Lond) (2016) 130 (23): 2139–2149.
Article history
Received:
June 21 2016
Revision Received:
August 26 2016
Accepted:
September 12 2016
Accepted Manuscript online:
September 13 2016
Citation
Idoia Gallego, Javier Beaumont, Begoña López, Susana Ravassa, Juan José Gómez-Doblas, María Ujué Moreno, Félix Valencia, Eduardo de Teresa, Javier Díez, Arantxa González; Potential role of microRNA-10b down-regulation in cardiomyocyte apoptosis in aortic stenosis patients. Clin Sci (Lond) 1 December 2016; 130 (23): 2139–2149. doi: https://doi.org/10.1042/CS20160462
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