- Email: [email protected]
Left ventricular dysfunction and heart failure manifestations in Duchenne muscular dystrophy
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Archives of Cardiovascular Diseases Supplements (2017) 9, 208-209
Topic 26 – Heart failure and cardiomyopathies + rehabilitation, exercises and prevention April 07th, Friday 2017
067 Lineage analysis of ventricular trabeculae to decipher the role of Nkx2-5 in conduction system development C. Choquet*, R. Kelly, L. Miquerol Aix-Marseille Université, CNRS UMR7288, IBDM, MARSEILLE, France *Corresponding author: [email protected] During cardiac development, transient invaginations of the myocardium, termed trabeculae, appear at the inner surface of the ventricles, and a subsequent compaction during fetal stages leads to a functional ventricular wall. Trabeculae contain progenitor cells of the ventricular conduction system (VCS), a complex network of Purkinje fibers (PF) that controls the rapid propagation of electrical activity in the ventricles. Defects in ventricular compaction and conduction have been observed in patients and mutant mice carrying mutations in NKX2-5, encoding a key transcriptional regulator of heart development. In order to analyze the link between trabecular fate and VCS differentiation, we carried out a genetic lineage analysis of trabecular fate using Cx40-CreERT2 mice expressing a tamoxifen-inducible Cre recombinase in ventricular trabeculae and in the definitive VCS. These mice were crossed with Rosa26-Confetti mice for a prospective clonal analysis of trabeculae. Our results show that cells exclusively fated to give rise to the VCS are present in the trabecular compartment as early as E9.5. Specification of new conductive cells within the trabecular compartment during subsequent development contributes progressively to the formation of a complex PF network at birth. We performed the same experiments in Nkx2-5 heterozygous mice with severe hypoplasia of the PF network at adult stages. The number of PFs originating from early Nkx2-5 haploinsufficient progenitors is identical to control. In contrast, we observed a progressive increase of trabecular cells that do not give rise to the VCS at later stage of development. This suggests that Nkx2-5 plays a role in the progressive recruitment of trabecular cells into the VCS as well as later in maintenance of the conductive phenotype. This study highlights the early segregation of the ventricular conduction system lineage at the onset of trabeculation and the role of Nkx2-5 at later stages of the formation of the PF network. The author hereby declares no conflict of interest
113 Bcl11b, a transcription factor: its role in transcriptional regulation of cardiac hypertrophy. M. Daher* (1), R. Riclet (2), O. Rohr (2), P. Bausero (1), P. Liu (3), Z. Li (1), A. Parlakian (1) (1) IBPS, Biological Adaptation and Ageing, UMR 8256, CNRS, INSERM U1164, Université Pierre et Marie Curie, Paris – (2) Institut de parasitologie et de pathologie tropicale, EA7292, Université de Strasbourg, Strasbourg, France – (3) Wellcome Trust Sanger Institute, Cambridge, Royaume-Uni *Corresponding author: [email protected] Diverse forms of cardiomyopathies result in cardiac compensatory remodeling that may progress to ventricular dilation and heart failure. This remodeling is characterized by an increase in the size of cardiomyocytes associated with elevated rates of RNA synthesis and the activation of foetal cardiac genes. It has been shown that Bcl11b, a zinc finger transcription factor, interacts with the RNApolymeraseII regulatory complex pTefb and exert an inhibitory action on it. Microarray data showed that Bcl11b could modulate the expression of genes during cardiac hypertrophy. Our aim is to determine the role of bcl11b in regulating transcription during cardiac homeostasis and hypertrophy. Through the use of various techniques (ChromatinIP, qPCR) we
© Elsevier Masson SAS. All rights reserved.
detected an enrichment of Bcl11b binding on the promoters of genes involved in cardiac hypertrophy (βMHC, skeletal and cardiac actin) as compared to control. This enrichment was correlated with an increase in the expression of the βMHC and skeletal actin genes and anti-correlated with the expression of the cardiac actin gene suggesting a dual role for Bcl11b (activator/inhibitor). Post-translational modifications of Bcl11b could explain this dual function. In order to gain further insight into the physiological role of Bcl11b in cardiac homeostasis and pathophysiology, we generated Bcl11b cardiac-specific KO mice and analysed the phenotype. Our first results showed that mice lacking Bcl11b in cardiomyocytes develop cardiac fibrosis and an up regulated expression of hypertrophy markers such as ANF and BNP. Future experiments will allow us to decipher the molecular mechanisms that govern the onset of pathological cardiac hypertrophy and more specifically the role of Bcl11b in this process. In the long term this study could pave the way for potential pharmacological approaches aiming to control and modulate the extent of cardiac hypertrophy and restore myocardial phenotype and function. The author hereby declares no conflict of interest
122 Temporal deletions of Nkx2-5 induce hypertrabeculation and progressive conduction defects and heart failure M. Nguyen (1-2), C. Choquet* (1), P. Sicard (3), F. Kober (4), I. Varlet (4), P. Rihet (2), S. Richard (3), C. Nguyen (2), M. Bernard (4), R. Kelly (1), N. Lalevée (2), L. Miquerol (1) (1) Aix-Marseille Université, CNRS, IBDM, MARSEILLE – (2) Aix-Marseille Université, INSERM, TAGC-UMR 1090, Marseille – (3) Université de Montpellier, CNRS, INSERM, PHYMEDEXP, CHU Arnaud de Villeneuve, Montpellier – (4) Aix-Marseille Université, CNRS, CRMBM, Marseille, France *Corresponding author: [email protected] Left ventricular non-compaction (LVNC), characterized by hypertrabeculation and deep trabecular recesses in the left ventricle, is the most common cardiomyopathy with a spectrum ranging from extreme normal variants to a pathological phenotype. In all forms, heart failure and sudden cardiac death represent the most severe complications related with non-compaction and arrhythmias. Defects in ventricular compaction and conduction are traits observed in patients and mutant mice carrying mutations in NKX2-5, encoding a key transcriptional regulator of cardiac development. In order to dissect the role of this gene in the apparition of the pathological outcomes of LVNC, we established a LVNC mouse model by inactivating Nkx2-5 in a time and tissue specific manner. Nkx2-5 was conditionally knockout in atria and trabecular cardiomyocytes at embryonic stages, when trabeculae arise, or during fetal stage, when they start to compact, or at neonatal stages, when the ventricles are mature. Our results show that the loss of Nkx2-5 at embryonic stages provokes a hypertrabeculation associated with important subendocardial fibrosis and Purkinje fibers hypoplasia in adult mice. These phenotypes are milder when the deletion occurred at fetal stages. Deletion only in the ventricular conduction system, at neonatal stage, leads to a progressive hypoplasia of this tissue without signs of hypertrabeculation nor fibrosis. However, all these mice develop progressively conduction defects and heart failure. The analysis of molecular pathways associated to these phenotypes, demonstrated that Nkx2-5 plays pleiotropic roles during trabecular development. Thus, deletion of Nkx2-5 during trabecular development represents a good model for studying the cellular and molecular mechanisms associated with LVNC, and the more pronounced disorder is provoked by a deletion at earlier stages. The author hereby declares no conflict of interest
286 Left ventricular dysfunction and heart failure manifestations in Duchenne muscular dystrophy F. Arhlade*, I. Nassiri, R. Habbal Cardiologie, chu ibn rochd, Casablanca, Maroc *Corresponding author: [email protected] Background Duchenne muscular dystrophy (DMD) is a severe X-linked disease due to loss of dystrophin in skeletal and cardiac muscle. Cardiomyo-
UntitledBook1.book Page 209 Monday, March 20, 2017 2:28 PM
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Archives of Cardiovascular Diseases Supplements (2017) 9, 208-209
pathy is a leading cause of death. Early use of ACE inhibitors and beta blockers improves the prognosis. Purpose The purpose of this study was to evaluate the relation between heart failure manifestations and left ventricular (LV) dysfunction in a group of patients with DMD and to look for early signs of LV impairment. Material and methods We evaluated 6 male patients with DMD, genetically verified, aged 20 to 40 years followed in care unit of CHF (mean± SD, 30 ±10 years). A clinical examination, 12-channel ECG, standard 2D, Doppler and tissue Doppler (TDI) echocardiography were performed. Results Dyspnea consistent with symptoms of heart failure was found in 2 patients (33%). The most common complaint was from palpitations. In all of the patients, sinus tachycardia was registered in one patient (HR>100 beats per minute), average heart rate 85 ±11.5 beats per minute. Average LV systolic function is 30%. One patient (33%) had LV diastolic dysfunction with elevated filing pressure. All of them have dilated cardiomyopathy with apical thrombus in one patient and one had severed mitral regurgitation. All of them were treated by b-blockers, spironolactone and ACE. Conclusion In boys with Duchenne muscular dystrophy there is a progressive decline in left ventricular systolic function. Heart failure manifestations are not so obvious, mainly because of the restricted physical activity and the accompanying respiratory failure. The author hereby declares no conflict of interest
ability of primary outcome was significantly greater in patients with GLS values poorer than – 17.2% (p=0.001). On multivariate analysis PR interval and GLS remained significantly and independently associated with the primary endpoint [hazard ratio (HR) 1.03, 95% confidence interval (CI) 1.01– 1.04, p=0.006] for PR interval and [HR 1.4, 95% CI 1.1–1.7, p=0.002] for GLS. Conclusion Left ventricular GLS is a powerful marker to predict cardiovascular events in DM1 patients. The author hereby declares no conflict of interest
077 Shared gene expression profile between aging and diseased hearts in man M. Steenman* (1), M. Stefani (2), N. Thebaud (1), V. Szüts (3), A. Varro (3), C. Dos Remedios (2), R. Houlgatte (4) (1) INSERM, UMR1087, l’institut du thorax, Nantes, France – (2) University of Sydney, Sydney, Australie – (3) Hungarian Academy of Sciences, Institute of Biochemistry, Biological Research Centre, Szeged, Hongrie – (4) INSERM U954, Faculty of Medicine, Nancy, France *Corresponding author: [email protected] Background Age is a major risk factor for cardiovascular disease, reflected by an increased prevalence with age of both heart failure (HF) and atrial fibrillation (AF). Data on molecular markers of human cardiac aging are lacking.
419 Left ventricular longitudinal strain predicts cardiovascular events in type 1 myotonic dystrophy. N. Bidegain* (1), C. Goujeau (1), Q. Labarre (1), P. Roumegou (1), P. Becat (2), M. Lesbordes (1), Y. Amzallag (1), B. Stordeur (1), F. Schaerer (1), F. Le Gal (1), B. Degand (1), L. Christiaens (1), R. Garcia (1) (1) Electrophysiologie et simulation cardiaque – (2) imagerie cardiaque, CHU et université, Poitiers, France *Corresponding author: [email protected] Introduction Type 1 myotonic dystrophy (DM1) patients' prognosis is very poor and is determined by respiratory and cardiac complications. Purpose The aim was to assess global longitudinal strain (GLS) prognostic value regarding cardiovascular events in DM1 patients. Methods DM1 patients were included between 2011 and 2015 and were followed up until January 2016. Patients underwent a transthoracic echocardiography at inclusion. The primary endpoint was a composite of all-cause mortality, type 2 Mobitz 2 and type 3 atrioventricular block, symptomatic sinoatrial block, HV interval ≥70 ms at invasive electrophysiology exploration, LVEF ≤45% and newly developed atrial fibrillation. Forty-six patients (25 males, mean age 40 years old) were included. The primary outcome happened in 14 patients during a mean follow-up of 38 months. Results GLS of patients who reached the primary endpoint was significantly impaired as compared to patients who didn’t (–15.1 [ – 16.7; –12.7]% vs. –18.2 [–19.2; –16.7]% respectively; p=0.001). The GLS cutoff value maximizing the likelihood ratio was –17.2% and survival curves showed that prob-
Purpose Our aim is to identify age-related gene expression changes in human left ventricle (LV) and left atrium (LA) and to analyze the data in the context of the age-related pathologies HF and AF. Methods RNA, obtained from 60 non-failing LV and 75 non-failing LA tissue samples, was hybridized to genome-wide microarrays. Aging-related functional annotations were identified by K-means clustering and Gene Ontology enrichment analysis (GoMiner). Statistically significantly agerelated genes were identified by quantitative Significance Analysis of Microarrays (SAM). Meta-analysis was performed on HF and AF gene expression datasets from the Gene Expression Omnibus database repository and results were compared to our cardiac age-related gene-lists. Results We identified 142 genes associated with age in the LV samples and 52 genes associated with age in the LA samples. In LV samples, “antigen-processing-and-presentation” and “electron-transport-chain” related transcripts were found to be enriched in K-means clusters down-regulated with age. Agerelated up-regulation corresponded with an enrichment of “adrenal-glanddevelopment” related transcripts. In LA samples, age-related down-regulation of gene expression was found to be related to transcription-associated gene ontologies, whereas the “transepithelial-transport” annotation was enriched in the upregulated K-means cluster. Meta-analysis identified some overlap between aging and HF gene expression profiles for LV tissue and between aging and AF gene expression profiles for atrial tissue. Conclusion The identified overlaps between cardiac aging and HF/AF profiles, may explain the molecular basis of the risk factor ‘aging’ in human cardiovascular disease. The author hereby declares no conflict of interest
© Elsevier Masson SAS. All rights reserved.
208
Archives of Cardiovascular Diseases Supplements (2017) 9, 208-209
Topic 26 – Heart failure and cardiomyopathies + rehabilitation, exercises and prevention April 07th, Friday 2017
067 Lineage analysis of ventricular trabeculae to decipher the role of Nkx2-5 in conduction system development C. Choquet*, R. Kelly, L. Miquerol Aix-Marseille Université, CNRS UMR7288, IBDM, MARSEILLE, France *Corresponding author: [email protected] During cardiac development, transient invaginations of the myocardium, termed trabeculae, appear at the inner surface of the ventricles, and a subsequent compaction during fetal stages leads to a functional ventricular wall. Trabeculae contain progenitor cells of the ventricular conduction system (VCS), a complex network of Purkinje fibers (PF) that controls the rapid propagation of electrical activity in the ventricles. Defects in ventricular compaction and conduction have been observed in patients and mutant mice carrying mutations in NKX2-5, encoding a key transcriptional regulator of heart development. In order to analyze the link between trabecular fate and VCS differentiation, we carried out a genetic lineage analysis of trabecular fate using Cx40-CreERT2 mice expressing a tamoxifen-inducible Cre recombinase in ventricular trabeculae and in the definitive VCS. These mice were crossed with Rosa26-Confetti mice for a prospective clonal analysis of trabeculae. Our results show that cells exclusively fated to give rise to the VCS are present in the trabecular compartment as early as E9.5. Specification of new conductive cells within the trabecular compartment during subsequent development contributes progressively to the formation of a complex PF network at birth. We performed the same experiments in Nkx2-5 heterozygous mice with severe hypoplasia of the PF network at adult stages. The number of PFs originating from early Nkx2-5 haploinsufficient progenitors is identical to control. In contrast, we observed a progressive increase of trabecular cells that do not give rise to the VCS at later stage of development. This suggests that Nkx2-5 plays a role in the progressive recruitment of trabecular cells into the VCS as well as later in maintenance of the conductive phenotype. This study highlights the early segregation of the ventricular conduction system lineage at the onset of trabeculation and the role of Nkx2-5 at later stages of the formation of the PF network. The author hereby declares no conflict of interest
113 Bcl11b, a transcription factor: its role in transcriptional regulation of cardiac hypertrophy. M. Daher* (1), R. Riclet (2), O. Rohr (2), P. Bausero (1), P. Liu (3), Z. Li (1), A. Parlakian (1) (1) IBPS, Biological Adaptation and Ageing, UMR 8256, CNRS, INSERM U1164, Université Pierre et Marie Curie, Paris – (2) Institut de parasitologie et de pathologie tropicale, EA7292, Université de Strasbourg, Strasbourg, France – (3) Wellcome Trust Sanger Institute, Cambridge, Royaume-Uni *Corresponding author: [email protected] Diverse forms of cardiomyopathies result in cardiac compensatory remodeling that may progress to ventricular dilation and heart failure. This remodeling is characterized by an increase in the size of cardiomyocytes associated with elevated rates of RNA synthesis and the activation of foetal cardiac genes. It has been shown that Bcl11b, a zinc finger transcription factor, interacts with the RNApolymeraseII regulatory complex pTefb and exert an inhibitory action on it. Microarray data showed that Bcl11b could modulate the expression of genes during cardiac hypertrophy. Our aim is to determine the role of bcl11b in regulating transcription during cardiac homeostasis and hypertrophy. Through the use of various techniques (ChromatinIP, qPCR) we
© Elsevier Masson SAS. All rights reserved.
detected an enrichment of Bcl11b binding on the promoters of genes involved in cardiac hypertrophy (βMHC, skeletal and cardiac actin) as compared to control. This enrichment was correlated with an increase in the expression of the βMHC and skeletal actin genes and anti-correlated with the expression of the cardiac actin gene suggesting a dual role for Bcl11b (activator/inhibitor). Post-translational modifications of Bcl11b could explain this dual function. In order to gain further insight into the physiological role of Bcl11b in cardiac homeostasis and pathophysiology, we generated Bcl11b cardiac-specific KO mice and analysed the phenotype. Our first results showed that mice lacking Bcl11b in cardiomyocytes develop cardiac fibrosis and an up regulated expression of hypertrophy markers such as ANF and BNP. Future experiments will allow us to decipher the molecular mechanisms that govern the onset of pathological cardiac hypertrophy and more specifically the role of Bcl11b in this process. In the long term this study could pave the way for potential pharmacological approaches aiming to control and modulate the extent of cardiac hypertrophy and restore myocardial phenotype and function. The author hereby declares no conflict of interest
122 Temporal deletions of Nkx2-5 induce hypertrabeculation and progressive conduction defects and heart failure M. Nguyen (1-2), C. Choquet* (1), P. Sicard (3), F. Kober (4), I. Varlet (4), P. Rihet (2), S. Richard (3), C. Nguyen (2), M. Bernard (4), R. Kelly (1), N. Lalevée (2), L. Miquerol (1) (1) Aix-Marseille Université, CNRS, IBDM, MARSEILLE – (2) Aix-Marseille Université, INSERM, TAGC-UMR 1090, Marseille – (3) Université de Montpellier, CNRS, INSERM, PHYMEDEXP, CHU Arnaud de Villeneuve, Montpellier – (4) Aix-Marseille Université, CNRS, CRMBM, Marseille, France *Corresponding author: [email protected] Left ventricular non-compaction (LVNC), characterized by hypertrabeculation and deep trabecular recesses in the left ventricle, is the most common cardiomyopathy with a spectrum ranging from extreme normal variants to a pathological phenotype. In all forms, heart failure and sudden cardiac death represent the most severe complications related with non-compaction and arrhythmias. Defects in ventricular compaction and conduction are traits observed in patients and mutant mice carrying mutations in NKX2-5, encoding a key transcriptional regulator of cardiac development. In order to dissect the role of this gene in the apparition of the pathological outcomes of LVNC, we established a LVNC mouse model by inactivating Nkx2-5 in a time and tissue specific manner. Nkx2-5 was conditionally knockout in atria and trabecular cardiomyocytes at embryonic stages, when trabeculae arise, or during fetal stage, when they start to compact, or at neonatal stages, when the ventricles are mature. Our results show that the loss of Nkx2-5 at embryonic stages provokes a hypertrabeculation associated with important subendocardial fibrosis and Purkinje fibers hypoplasia in adult mice. These phenotypes are milder when the deletion occurred at fetal stages. Deletion only in the ventricular conduction system, at neonatal stage, leads to a progressive hypoplasia of this tissue without signs of hypertrabeculation nor fibrosis. However, all these mice develop progressively conduction defects and heart failure. The analysis of molecular pathways associated to these phenotypes, demonstrated that Nkx2-5 plays pleiotropic roles during trabecular development. Thus, deletion of Nkx2-5 during trabecular development represents a good model for studying the cellular and molecular mechanisms associated with LVNC, and the more pronounced disorder is provoked by a deletion at earlier stages. The author hereby declares no conflict of interest
286 Left ventricular dysfunction and heart failure manifestations in Duchenne muscular dystrophy F. Arhlade*, I. Nassiri, R. Habbal Cardiologie, chu ibn rochd, Casablanca, Maroc *Corresponding author: [email protected] Background Duchenne muscular dystrophy (DMD) is a severe X-linked disease due to loss of dystrophin in skeletal and cardiac muscle. Cardiomyo-
UntitledBook1.book Page 209 Monday, March 20, 2017 2:28 PM
209
Archives of Cardiovascular Diseases Supplements (2017) 9, 208-209
pathy is a leading cause of death. Early use of ACE inhibitors and beta blockers improves the prognosis. Purpose The purpose of this study was to evaluate the relation between heart failure manifestations and left ventricular (LV) dysfunction in a group of patients with DMD and to look for early signs of LV impairment. Material and methods We evaluated 6 male patients with DMD, genetically verified, aged 20 to 40 years followed in care unit of CHF (mean± SD, 30 ±10 years). A clinical examination, 12-channel ECG, standard 2D, Doppler and tissue Doppler (TDI) echocardiography were performed. Results Dyspnea consistent with symptoms of heart failure was found in 2 patients (33%). The most common complaint was from palpitations. In all of the patients, sinus tachycardia was registered in one patient (HR>100 beats per minute), average heart rate 85 ±11.5 beats per minute. Average LV systolic function is 30%. One patient (33%) had LV diastolic dysfunction with elevated filing pressure. All of them have dilated cardiomyopathy with apical thrombus in one patient and one had severed mitral regurgitation. All of them were treated by b-blockers, spironolactone and ACE. Conclusion In boys with Duchenne muscular dystrophy there is a progressive decline in left ventricular systolic function. Heart failure manifestations are not so obvious, mainly because of the restricted physical activity and the accompanying respiratory failure. The author hereby declares no conflict of interest
ability of primary outcome was significantly greater in patients with GLS values poorer than – 17.2% (p=0.001). On multivariate analysis PR interval and GLS remained significantly and independently associated with the primary endpoint [hazard ratio (HR) 1.03, 95% confidence interval (CI) 1.01– 1.04, p=0.006] for PR interval and [HR 1.4, 95% CI 1.1–1.7, p=0.002] for GLS. Conclusion Left ventricular GLS is a powerful marker to predict cardiovascular events in DM1 patients. The author hereby declares no conflict of interest
077 Shared gene expression profile between aging and diseased hearts in man M. Steenman* (1), M. Stefani (2), N. Thebaud (1), V. Szüts (3), A. Varro (3), C. Dos Remedios (2), R. Houlgatte (4) (1) INSERM, UMR1087, l’institut du thorax, Nantes, France – (2) University of Sydney, Sydney, Australie – (3) Hungarian Academy of Sciences, Institute of Biochemistry, Biological Research Centre, Szeged, Hongrie – (4) INSERM U954, Faculty of Medicine, Nancy, France *Corresponding author: [email protected] Background Age is a major risk factor for cardiovascular disease, reflected by an increased prevalence with age of both heart failure (HF) and atrial fibrillation (AF). Data on molecular markers of human cardiac aging are lacking.
419 Left ventricular longitudinal strain predicts cardiovascular events in type 1 myotonic dystrophy. N. Bidegain* (1), C. Goujeau (1), Q. Labarre (1), P. Roumegou (1), P. Becat (2), M. Lesbordes (1), Y. Amzallag (1), B. Stordeur (1), F. Schaerer (1), F. Le Gal (1), B. Degand (1), L. Christiaens (1), R. Garcia (1) (1) Electrophysiologie et simulation cardiaque – (2) imagerie cardiaque, CHU et université, Poitiers, France *Corresponding author: [email protected] Introduction Type 1 myotonic dystrophy (DM1) patients' prognosis is very poor and is determined by respiratory and cardiac complications. Purpose The aim was to assess global longitudinal strain (GLS) prognostic value regarding cardiovascular events in DM1 patients. Methods DM1 patients were included between 2011 and 2015 and were followed up until January 2016. Patients underwent a transthoracic echocardiography at inclusion. The primary endpoint was a composite of all-cause mortality, type 2 Mobitz 2 and type 3 atrioventricular block, symptomatic sinoatrial block, HV interval ≥70 ms at invasive electrophysiology exploration, LVEF ≤45% and newly developed atrial fibrillation. Forty-six patients (25 males, mean age 40 years old) were included. The primary outcome happened in 14 patients during a mean follow-up of 38 months. Results GLS of patients who reached the primary endpoint was significantly impaired as compared to patients who didn’t (–15.1 [ – 16.7; –12.7]% vs. –18.2 [–19.2; –16.7]% respectively; p=0.001). The GLS cutoff value maximizing the likelihood ratio was –17.2% and survival curves showed that prob-
Purpose Our aim is to identify age-related gene expression changes in human left ventricle (LV) and left atrium (LA) and to analyze the data in the context of the age-related pathologies HF and AF. Methods RNA, obtained from 60 non-failing LV and 75 non-failing LA tissue samples, was hybridized to genome-wide microarrays. Aging-related functional annotations were identified by K-means clustering and Gene Ontology enrichment analysis (GoMiner). Statistically significantly agerelated genes were identified by quantitative Significance Analysis of Microarrays (SAM). Meta-analysis was performed on HF and AF gene expression datasets from the Gene Expression Omnibus database repository and results were compared to our cardiac age-related gene-lists. Results We identified 142 genes associated with age in the LV samples and 52 genes associated with age in the LA samples. In LV samples, “antigen-processing-and-presentation” and “electron-transport-chain” related transcripts were found to be enriched in K-means clusters down-regulated with age. Agerelated up-regulation corresponded with an enrichment of “adrenal-glanddevelopment” related transcripts. In LA samples, age-related down-regulation of gene expression was found to be related to transcription-associated gene ontologies, whereas the “transepithelial-transport” annotation was enriched in the upregulated K-means cluster. Meta-analysis identified some overlap between aging and HF gene expression profiles for LV tissue and between aging and AF gene expression profiles for atrial tissue. Conclusion The identified overlaps between cardiac aging and HF/AF profiles, may explain the molecular basis of the risk factor ‘aging’ in human cardiovascular disease. The author hereby declares no conflict of interest
© Elsevier Masson SAS. All rights reserved.