Cargando…
ASB1 differential methylation in ischaemic cardiomyopathy: relationship with left ventricular performance in end‐stage heart failure patients
AIMS: Ischaemic cardiomyopathy (ICM) leads to impaired contraction and ventricular dysfunction, causing high rates of morbidity and mortality. Epigenomics allows the identification of epigenetic signatures in human diseases. We analyse the differential epigenetic patterns of the ASB gene family in I...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6073036/ https://www.ncbi.nlm.nih.gov/pubmed/29667349 http://dx.doi.org/10.1002/ehf2.12289 |
_version_ | 1783344103437631488 |
---|---|
author | Ortega, Ana Tarazón, Estefanía Gil‐Cayuela, Carolina Martínez‐Dolz, Luis Lago, Francisca González‐Juanatey, José Ramón Sandoval, Juan Portolés, Manuel Roselló‐Lletí, Esther Rivera, Miguel |
author_facet | Ortega, Ana Tarazón, Estefanía Gil‐Cayuela, Carolina Martínez‐Dolz, Luis Lago, Francisca González‐Juanatey, José Ramón Sandoval, Juan Portolés, Manuel Roselló‐Lletí, Esther Rivera, Miguel |
author_sort | Ortega, Ana |
collection | PubMed |
description | AIMS: Ischaemic cardiomyopathy (ICM) leads to impaired contraction and ventricular dysfunction, causing high rates of morbidity and mortality. Epigenomics allows the identification of epigenetic signatures in human diseases. We analyse the differential epigenetic patterns of the ASB gene family in ICM patients and relate these alterations to their haemodynamic and functional status. METHODS AND RESULTS: Epigenomic analysis was carried out using 16 left ventricular (LV) tissue samples, eight from ICM patients undergoing heart transplantation and eight from control (CNT) subjects without cardiac disease. We increased the sample size up to 13 ICM and 10 CNT for RNA sequencing and to 14 ICM for pyrosequencing analyses. We found a hypermethylated profile (cg11189868) in the ASB1 gene that showed a differential methylation of 0.26Δβ (P = 0.016). This result was validated by a pyrosequencing technique (0.23Δβ, P = 0.048). Notably, the methylation pattern was strongly related to LV ejection fraction (r = −0.849, P = 0.008), stroke volume (r = −0.929, P = 0.001), and end‐systolic and diastolic LV diameters (r = −0.743, P = 0.035 for both). ASB1 showed a down‐regulation in messenger RNA levels (−1.2‐fold, P = 0.039). CONCLUSIONS: Our findings link a specific ASB1 methylation pattern to LV structure and performance in end‐stage ICM, opening new therapeutic opportunities and providing new insights regarding which is the functionally relevant genome in the ischaemic failing myocardium. |
format | Online Article Text |
id | pubmed-6073036 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-60730362018-08-07 ASB1 differential methylation in ischaemic cardiomyopathy: relationship with left ventricular performance in end‐stage heart failure patients Ortega, Ana Tarazón, Estefanía Gil‐Cayuela, Carolina Martínez‐Dolz, Luis Lago, Francisca González‐Juanatey, José Ramón Sandoval, Juan Portolés, Manuel Roselló‐Lletí, Esther Rivera, Miguel ESC Heart Fail Short Communications AIMS: Ischaemic cardiomyopathy (ICM) leads to impaired contraction and ventricular dysfunction, causing high rates of morbidity and mortality. Epigenomics allows the identification of epigenetic signatures in human diseases. We analyse the differential epigenetic patterns of the ASB gene family in ICM patients and relate these alterations to their haemodynamic and functional status. METHODS AND RESULTS: Epigenomic analysis was carried out using 16 left ventricular (LV) tissue samples, eight from ICM patients undergoing heart transplantation and eight from control (CNT) subjects without cardiac disease. We increased the sample size up to 13 ICM and 10 CNT for RNA sequencing and to 14 ICM for pyrosequencing analyses. We found a hypermethylated profile (cg11189868) in the ASB1 gene that showed a differential methylation of 0.26Δβ (P = 0.016). This result was validated by a pyrosequencing technique (0.23Δβ, P = 0.048). Notably, the methylation pattern was strongly related to LV ejection fraction (r = −0.849, P = 0.008), stroke volume (r = −0.929, P = 0.001), and end‐systolic and diastolic LV diameters (r = −0.743, P = 0.035 for both). ASB1 showed a down‐regulation in messenger RNA levels (−1.2‐fold, P = 0.039). CONCLUSIONS: Our findings link a specific ASB1 methylation pattern to LV structure and performance in end‐stage ICM, opening new therapeutic opportunities and providing new insights regarding which is the functionally relevant genome in the ischaemic failing myocardium. John Wiley and Sons Inc. 2018-04-17 /pmc/articles/PMC6073036/ /pubmed/29667349 http://dx.doi.org/10.1002/ehf2.12289 Text en © 2018 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Short Communications Ortega, Ana Tarazón, Estefanía Gil‐Cayuela, Carolina Martínez‐Dolz, Luis Lago, Francisca González‐Juanatey, José Ramón Sandoval, Juan Portolés, Manuel Roselló‐Lletí, Esther Rivera, Miguel ASB1 differential methylation in ischaemic cardiomyopathy: relationship with left ventricular performance in end‐stage heart failure patients |
title |
ASB1 differential methylation in ischaemic cardiomyopathy: relationship with left ventricular performance in end‐stage heart failure patients |
title_full |
ASB1 differential methylation in ischaemic cardiomyopathy: relationship with left ventricular performance in end‐stage heart failure patients |
title_fullStr |
ASB1 differential methylation in ischaemic cardiomyopathy: relationship with left ventricular performance in end‐stage heart failure patients |
title_full_unstemmed |
ASB1 differential methylation in ischaemic cardiomyopathy: relationship with left ventricular performance in end‐stage heart failure patients |
title_short |
ASB1 differential methylation in ischaemic cardiomyopathy: relationship with left ventricular performance in end‐stage heart failure patients |
title_sort | asb1 differential methylation in ischaemic cardiomyopathy: relationship with left ventricular performance in end‐stage heart failure patients |
topic | Short Communications |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6073036/ https://www.ncbi.nlm.nih.gov/pubmed/29667349 http://dx.doi.org/10.1002/ehf2.12289 |
work_keys_str_mv | AT ortegaana asb1differentialmethylationinischaemiccardiomyopathyrelationshipwithleftventricularperformanceinendstageheartfailurepatients AT tarazonestefania asb1differentialmethylationinischaemiccardiomyopathyrelationshipwithleftventricularperformanceinendstageheartfailurepatients AT gilcayuelacarolina asb1differentialmethylationinischaemiccardiomyopathyrelationshipwithleftventricularperformanceinendstageheartfailurepatients AT martinezdolzluis asb1differentialmethylationinischaemiccardiomyopathyrelationshipwithleftventricularperformanceinendstageheartfailurepatients AT lagofrancisca asb1differentialmethylationinischaemiccardiomyopathyrelationshipwithleftventricularperformanceinendstageheartfailurepatients AT gonzalezjuanateyjoseramon asb1differentialmethylationinischaemiccardiomyopathyrelationshipwithleftventricularperformanceinendstageheartfailurepatients AT sandovaljuan asb1differentialmethylationinischaemiccardiomyopathyrelationshipwithleftventricularperformanceinendstageheartfailurepatients AT portolesmanuel asb1differentialmethylationinischaemiccardiomyopathyrelationshipwithleftventricularperformanceinendstageheartfailurepatients AT rosellolletiesther asb1differentialmethylationinischaemiccardiomyopathyrelationshipwithleftventricularperformanceinendstageheartfailurepatients AT riveramiguel asb1differentialmethylationinischaemiccardiomyopathyrelationshipwithleftventricularperformanceinendstageheartfailurepatients |