Cargando…

ACE-inhibition induces a cardioprotective transcriptional response in the metabolic syndrome heart

Cardiovascular disease associated with metabolic syndrome has a high prevalence, but the mechanistic basis of metabolic cardiomyopathy remains poorly understood. We characterised the cardiac transcriptome in a murine metabolic syndrome (MetS) model (LDLR−/−; ob/ob, DKO) relative to the healthy, cont...

Descripción completa

Detalles Bibliográficos
Autores principales: Yakubova, Aziza, Thorrez, Lieven, Svetlichnyy, Dmitry, Zwarts, Liesbeth, Vulsteke, Veerle, Laenen, Griet, Oosterlinck, Wouter, Moreau, Yves, Dehaspe, Luc, Van Houdt, Jeroen, Cortés-Calabuig, Álvaro, De Moor, Bart, Callaerts, Patrick, Herijgers, Paul
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6212468/
https://www.ncbi.nlm.nih.gov/pubmed/30385846
http://dx.doi.org/10.1038/s41598-018-34547-9
_version_ 1783367544039538688
author Yakubova, Aziza
Thorrez, Lieven
Svetlichnyy, Dmitry
Zwarts, Liesbeth
Vulsteke, Veerle
Laenen, Griet
Oosterlinck, Wouter
Moreau, Yves
Dehaspe, Luc
Van Houdt, Jeroen
Cortés-Calabuig, Álvaro
De Moor, Bart
Callaerts, Patrick
Herijgers, Paul
author_facet Yakubova, Aziza
Thorrez, Lieven
Svetlichnyy, Dmitry
Zwarts, Liesbeth
Vulsteke, Veerle
Laenen, Griet
Oosterlinck, Wouter
Moreau, Yves
Dehaspe, Luc
Van Houdt, Jeroen
Cortés-Calabuig, Álvaro
De Moor, Bart
Callaerts, Patrick
Herijgers, Paul
author_sort Yakubova, Aziza
collection PubMed
description Cardiovascular disease associated with metabolic syndrome has a high prevalence, but the mechanistic basis of metabolic cardiomyopathy remains poorly understood. We characterised the cardiac transcriptome in a murine metabolic syndrome (MetS) model (LDLR−/−; ob/ob, DKO) relative to the healthy, control heart (C57BL/6, WT) and the transcriptional changes induced by ACE-inhibition in those hearts. RNA-Seq, differential gene expression and transcription factor analysis identified 288 genes differentially expressed between DKO and WT hearts implicating 72 pathways. Hallmarks of metabolic cardiomyopathy were increased activity in integrin-linked kinase signalling, Rho signalling, dendritic cell maturation, production of nitric oxide and reactive oxygen species in macrophages, atherosclerosis, LXR-RXR signalling, cardiac hypertrophy, and acute phase response pathways. ACE-inhibition had a limited effect on gene expression in WT (55 genes, 23 pathways), and a prominent effect in DKO hearts (1143 genes, 104 pathways). In DKO hearts, ACE-I appears to counteract some of the MetS-specific pathways, while also activating cardioprotective mechanisms. We conclude that MetS and control murine hearts have unique transcriptional profiles and exhibit a partially specific transcriptional response to ACE-inhibition.
format Online
Article
Text
id pubmed-6212468
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-62124682018-11-06 ACE-inhibition induces a cardioprotective transcriptional response in the metabolic syndrome heart Yakubova, Aziza Thorrez, Lieven Svetlichnyy, Dmitry Zwarts, Liesbeth Vulsteke, Veerle Laenen, Griet Oosterlinck, Wouter Moreau, Yves Dehaspe, Luc Van Houdt, Jeroen Cortés-Calabuig, Álvaro De Moor, Bart Callaerts, Patrick Herijgers, Paul Sci Rep Article Cardiovascular disease associated with metabolic syndrome has a high prevalence, but the mechanistic basis of metabolic cardiomyopathy remains poorly understood. We characterised the cardiac transcriptome in a murine metabolic syndrome (MetS) model (LDLR−/−; ob/ob, DKO) relative to the healthy, control heart (C57BL/6, WT) and the transcriptional changes induced by ACE-inhibition in those hearts. RNA-Seq, differential gene expression and transcription factor analysis identified 288 genes differentially expressed between DKO and WT hearts implicating 72 pathways. Hallmarks of metabolic cardiomyopathy were increased activity in integrin-linked kinase signalling, Rho signalling, dendritic cell maturation, production of nitric oxide and reactive oxygen species in macrophages, atherosclerosis, LXR-RXR signalling, cardiac hypertrophy, and acute phase response pathways. ACE-inhibition had a limited effect on gene expression in WT (55 genes, 23 pathways), and a prominent effect in DKO hearts (1143 genes, 104 pathways). In DKO hearts, ACE-I appears to counteract some of the MetS-specific pathways, while also activating cardioprotective mechanisms. We conclude that MetS and control murine hearts have unique transcriptional profiles and exhibit a partially specific transcriptional response to ACE-inhibition. Nature Publishing Group UK 2018-11-01 /pmc/articles/PMC6212468/ /pubmed/30385846 http://dx.doi.org/10.1038/s41598-018-34547-9 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Yakubova, Aziza
Thorrez, Lieven
Svetlichnyy, Dmitry
Zwarts, Liesbeth
Vulsteke, Veerle
Laenen, Griet
Oosterlinck, Wouter
Moreau, Yves
Dehaspe, Luc
Van Houdt, Jeroen
Cortés-Calabuig, Álvaro
De Moor, Bart
Callaerts, Patrick
Herijgers, Paul
ACE-inhibition induces a cardioprotective transcriptional response in the metabolic syndrome heart
title ACE-inhibition induces a cardioprotective transcriptional response in the metabolic syndrome heart
title_full ACE-inhibition induces a cardioprotective transcriptional response in the metabolic syndrome heart
title_fullStr ACE-inhibition induces a cardioprotective transcriptional response in the metabolic syndrome heart
title_full_unstemmed ACE-inhibition induces a cardioprotective transcriptional response in the metabolic syndrome heart
title_short ACE-inhibition induces a cardioprotective transcriptional response in the metabolic syndrome heart
title_sort ace-inhibition induces a cardioprotective transcriptional response in the metabolic syndrome heart
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6212468/
https://www.ncbi.nlm.nih.gov/pubmed/30385846
http://dx.doi.org/10.1038/s41598-018-34547-9
work_keys_str_mv AT yakubovaaziza aceinhibitioninducesacardioprotectivetranscriptionalresponseinthemetabolicsyndromeheart
AT thorrezlieven aceinhibitioninducesacardioprotectivetranscriptionalresponseinthemetabolicsyndromeheart
AT svetlichnyydmitry aceinhibitioninducesacardioprotectivetranscriptionalresponseinthemetabolicsyndromeheart
AT zwartsliesbeth aceinhibitioninducesacardioprotectivetranscriptionalresponseinthemetabolicsyndromeheart
AT vulstekeveerle aceinhibitioninducesacardioprotectivetranscriptionalresponseinthemetabolicsyndromeheart
AT laenengriet aceinhibitioninducesacardioprotectivetranscriptionalresponseinthemetabolicsyndromeheart
AT oosterlinckwouter aceinhibitioninducesacardioprotectivetranscriptionalresponseinthemetabolicsyndromeheart
AT moreauyves aceinhibitioninducesacardioprotectivetranscriptionalresponseinthemetabolicsyndromeheart
AT dehaspeluc aceinhibitioninducesacardioprotectivetranscriptionalresponseinthemetabolicsyndromeheart
AT vanhoudtjeroen aceinhibitioninducesacardioprotectivetranscriptionalresponseinthemetabolicsyndromeheart
AT cortescalabuigalvaro aceinhibitioninducesacardioprotectivetranscriptionalresponseinthemetabolicsyndromeheart
AT demoorbart aceinhibitioninducesacardioprotectivetranscriptionalresponseinthemetabolicsyndromeheart
AT callaertspatrick aceinhibitioninducesacardioprotectivetranscriptionalresponseinthemetabolicsyndromeheart
AT herijgerspaul aceinhibitioninducesacardioprotectivetranscriptionalresponseinthemetabolicsyndromeheart