title: Identification of Region-Specific Myocardial Gene Expression Patterns in a Chronic Swine Model of Repaired Tetralogy of Fallot.
abstract: Surgical repair of Tetralogy of Fallot (TOF) is highly successful but may be complicated in adulthood by arrhythmias, sudden death, and right ventricular or biventricular dysfunction. To better understand the molecular and cellular mechanisms of these delayed cardiac events, a chronic animal model of postoperative TOF was studied using microarrays to perform cardiac transcriptomic studies. The experimental study included 12 piglets (7 rTOF and 5 controls) that underwent surgery at age 2 months and were further studied after 23 (+/- 1) weeks of postoperative recovery. Two distinct regions (endocardium and epicardium) from both ventricles were analyzed. Expression levels from each localization were compared in order to decipher mechanisms and signaling pathways leading to ventricular dysfunction and arrhythmias in surgically repaired TOF. Several genes were confirmed to participate in ventricular remodeling and cardiac failure and some new candidate genes were described. In particular, these data pointed out FRZB as a heart failure marker. Moreover, calcium handling and contractile function genes (SLN, ACTC1, PLCD4, PLCZ), potential arrhythmia-related genes (MYO5B, KCNA5), and cytoskeleton and cellular organization-related genes (XIRP2, COL8A1, KCNA6) were among the most deregulated genes in rTOF ventricles. To our knowledge, this is the first comprehensive report on global gene expression profiling in the heart of a long-term swine model of repaired TOF.
authors.affiliation: L'Institut de Rythmologie et Modélisation Cardiaque LIRYC, Université de Bordeaux, Pessac, France; Inserm U1045 CRCTB, Université de Bordeaux, Bordeaux, France.
authors.forename: Sabine
authors.initials: S
authors.lastname: Charron
authors.affiliation: L'Institut de Rythmologie et Modélisation Cardiaque LIRYC, Université de Bordeaux, Pessac, France; Inserm U1045 CRCTB, Université de Bordeaux, Bordeaux, France; Hôpital cardiologique Haut-Lévêque, CHU de Bordeaux, Pessac, France.
authors.forename: François
authors.initials: F
authors.lastname: Roubertie
authors.affiliation: L'Institut de Rythmologie et Modélisation Cardiaque LIRYC, Université de Bordeaux, Pessac, France; Inserm U1045 CRCTB, Université de Bordeaux, Bordeaux, France.
authors.forename: David
authors.initials: D
authors.lastname: Benoist
authors.affiliation: L'Institut de Rythmologie et Modélisation Cardiaque LIRYC, Université de Bordeaux, Pessac, France; Inserm U1045 CRCTB, Université de Bordeaux, Bordeaux, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Dubes
authors.affiliation: L'Institut de Rythmologie et Modélisation Cardiaque LIRYC, Université de Bordeaux, Pessac, France; Inserm U1045 CRCTB, Université de Bordeaux, Bordeaux, France; Max Delbrück Center for Molecular Medicine, Berlin, Germany.
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Gilbert
authors.affiliation: L'Institut de Rythmologie et Modélisation Cardiaque LIRYC, Université de Bordeaux, Pessac, France; Inserm U1045 CRCTB, Université de Bordeaux, Bordeaux, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Constantin
authors.affiliation: Plateforme Technologique d'Innovation Biomédicale, Université de Bordeaux, Pessac, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Vieillot
authors.affiliation: L'Institut de Rythmologie et Modélisation Cardiaque LIRYC, Université de Bordeaux, Pessac, France; Inserm U1045 CRCTB, Université de Bordeaux, Bordeaux, France; University of Oxford, Institute of Biomedical Engineering, Oxford, United-Kingdom.
authors.forename: Delphine
authors.initials: D
authors.lastname: Elbes
authors.affiliation: L'Institut de Rythmologie et Modélisation Cardiaque LIRYC, Université de Bordeaux, Pessac, France; Inserm U1045 CRCTB, Université de Bordeaux, Bordeaux, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Quesson
authors.affiliation: L'Institut de Rythmologie et Modélisation Cardiaque LIRYC, Université de Bordeaux, Pessac, France; Inserm U1045 CRCTB, Université de Bordeaux, Bordeaux, France; Hôpital cardiologique Haut-Lévêque, CHU de Bordeaux, Pessac, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Bordachar
authors.affiliation: L'Institut de Rythmologie et Modélisation Cardiaque LIRYC, Université de Bordeaux, Pessac, France; Inserm U1045 CRCTB, Université de Bordeaux, Bordeaux, France; Hôpital cardiologique Haut-Lévêque, CHU de Bordeaux, Pessac, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Haissaguerre
authors.affiliation: L'Institut de Rythmologie et Modélisation Cardiaque LIRYC, Université de Bordeaux, Pessac, France; Inserm U1045 CRCTB, Université de Bordeaux, Bordeaux, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Bernus
authors.affiliation: L'Institut de Rythmologie et Modélisation Cardiaque LIRYC, Université de Bordeaux, Pessac, France; Inserm U1045 CRCTB, Université de Bordeaux, Bordeaux, France; Hôpital cardiologique Haut-Lévêque, CHU de Bordeaux, Pessac, France.
authors.forename: Jean-Benoit
authors.initials: JB
authors.lastname: Thambo
authors.affiliation: L'Institut de Rythmologie et Modélisation Cardiaque LIRYC, Université de Bordeaux, Pessac, France; Hôpital cardiologique Haut-Lévêque, CHU de Bordeaux, Pessac, France; Laboratoire Maladies Rares: Génétique et Métabolisme (MRGM), EA 4576, Université de Bordeaux, Bordeaux, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Rooryck
mesh_terms: D000818:Animals; D002908:Chronic Disease; D004195:Disease Models, Animal; D004699:Endocardium / Q000473:pathology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D063990:Gene Ontology; D053263:Gene Regulatory Networks; D056726:Genetic Association Studies; D006352:Heart Ventricles / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D009928:Organ Specificity / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D015203:Reproducibility of Results; D034421:Sus scrofa; D013771:Tetralogy of Fallot / Q000235:genetics* / Q000601:surgery*