1. ACE-inhibition induces a cardioprotective transcriptional response in the metabolic syndrome heart
- Author
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Bart De Moor, Luc Dehaspe, Veerle Vulsteke, Aziza Yakubova, Álvaro Cortés-Calabuig, Wouter Oosterlinck, Jeroen Van Houdt, Dmitry Svetlichnyy, Patrick Callaerts, Paul Herijgers, Lieven Thorrez, Liesbeth Zwarts, Griet Laenen, and Yves Moreau
- Subjects
0301 basic medicine ,lcsh:Medicine ,Angiotensin-Converting Enzyme Inhibitors ,030204 cardiovascular system & hematology ,Transcriptome ,Mice ,chemistry.chemical_compound ,0302 clinical medicine ,Gene expression ,CONVERTING ENZYME-INHIBITION ,Receptor ,CARDIAC-HYPERTROPHY ,lcsh:Science ,IN-VIVO ,Metabolic Syndrome ,Mice, Knockout ,chemistry.chemical_classification ,Multidisciplinary ,LIGHT-CHAIN ,Kinase ,Heart ,Cell biology ,Multidisciplinary Sciences ,Cardiovascular Diseases ,OBESITY ,Science & Technology - Other Topics ,Metabolic Networks and Pathways ,EXPRESSION ,Cardiotonic Agents ,Peptidyl-Dipeptidase A ,Biology ,Article ,Nitric oxide ,MECHANISMS ,03 medical and health sciences ,DIABETIC CARDIOMYOPATHY ,Animals ,Humans ,Obesity ,Gene ,Transcription factor ,Aged ,Reactive oxygen species ,Science & Technology ,lcsh:R ,Atherosclerosis ,GENE ,DYSFUNCTION ,Disease Models, Animal ,030104 developmental biology ,Receptors, LDL ,chemistry ,lcsh:Q - Abstract
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. ispartof: SCIENTIFIC REPORTS vol:8 issue:1 ispartof: location:England status: published
- Published
- 2018