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Identification of region-specific myocardial gene expression patterns in a chronic swine model of repaired tetralogy of fallot

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Item Type:Article
Title:Identification of region-specific myocardial gene expression patterns in a chronic swine model of repaired tetralogy of fallot
Creators Name:Charron, S. and Roubertie, F. and Benoist, D. and Dubes, V. and Gilbert, S.H. and Constantin, M. and Vieillot, D. and Elbes, D. and Quesson, B. and Bordachar, P. and Haissaguerre, M. and Bernus, O. and Thambo, J.B. and Rooryck, C.
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.
Keywords:Animal Disease Models, Chronic Disease, Endocardium, Gene Expression Profiling, Gene Expression Regulation, Gene Ontology, Gene Regulatory Networks, Genetic Association Studies, Heart Ventricles, Myocardium, Oligonucleotide Array Sequence Analysis, Organ Specificity, Real-Time Polymerase Chain Reaction, Reproducibility of Results, Tetralogy of Fallot, Animals, Sus scrofa
Source:PLoS ONE
Publisher:Public Library of Science
Page Range:e0134146
Date:7 August 2015
Official Publication:https://doi.org/10.1371/journal.pone.0134146
PubMed:View item in PubMed

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