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Identification of Region-Specific Myocardial Gene Expression Patterns in a Chronic Swine Model of Repaired Tetralogy of Fallot.

Charron S, Roubertie F, Benoist D, Dubes V, Gilbert SH, Constantin M, Vieillot D, Elbes D, Quesson B, Bordachar P, Haissaguerre M, Bernus O, Thambo JB, Rooryck C - PLoS ONE (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: L'Institut de Rythmologie et Modélisation Cardiaque LIRYC, Université de Bordeaux, Pessac, France; Inserm U1045 CRCTB, Université de Bordeaux, Bordeaux, France.

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.

No MeSH data available.


Related in: MedlinePlus

Relative expression (RT-qPCR) of genes in control (open bars) and Fallots (closed bars) pigs’ hearts and Fold change comparison between samples of the four localizations.Transcript expression is normalized to the reference genes HPRT1 and GUSB. Two sided T-Test Statistical significance of n = 5 Controls and n = 7 rTOF hearts (*P <0.05, **P <0.01, ***P <0.001).
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pone.0134146.g007: Relative expression (RT-qPCR) of genes in control (open bars) and Fallots (closed bars) pigs’ hearts and Fold change comparison between samples of the four localizations.Transcript expression is normalized to the reference genes HPRT1 and GUSB. Two sided T-Test Statistical significance of n = 5 Controls and n = 7 rTOF hearts (*P <0.05, **P <0.01, ***P <0.001).

Mentions: We then used a candidate gene approach and studied, by quantitative RT-PCR, samples from the four localizations by testing 5 genes: FRZB, PLCZ, TNNT1, XIRP2 and ACTC1 (Fig 7). Surprisingly, we observed significant deregulation of these genes in the four localizations but with a lower FC. This could be due to the much higher sensitivity of qPCR compared to microarray.


Identification of Region-Specific Myocardial Gene Expression Patterns in a Chronic Swine Model of Repaired Tetralogy of Fallot.

Charron S, Roubertie F, Benoist D, Dubes V, Gilbert SH, Constantin M, Vieillot D, Elbes D, Quesson B, Bordachar P, Haissaguerre M, Bernus O, Thambo JB, Rooryck C - PLoS ONE (2015)

Relative expression (RT-qPCR) of genes in control (open bars) and Fallots (closed bars) pigs’ hearts and Fold change comparison between samples of the four localizations.Transcript expression is normalized to the reference genes HPRT1 and GUSB. Two sided T-Test Statistical significance of n = 5 Controls and n = 7 rTOF hearts (*P <0.05, **P <0.01, ***P <0.001).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4529093&req=5

pone.0134146.g007: Relative expression (RT-qPCR) of genes in control (open bars) and Fallots (closed bars) pigs’ hearts and Fold change comparison between samples of the four localizations.Transcript expression is normalized to the reference genes HPRT1 and GUSB. Two sided T-Test Statistical significance of n = 5 Controls and n = 7 rTOF hearts (*P <0.05, **P <0.01, ***P <0.001).
Mentions: We then used a candidate gene approach and studied, by quantitative RT-PCR, samples from the four localizations by testing 5 genes: FRZB, PLCZ, TNNT1, XIRP2 and ACTC1 (Fig 7). Surprisingly, we observed significant deregulation of these genes in the four localizations but with a lower FC. This could be due to the much higher sensitivity of qPCR compared to microarray.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: L'Institut de Rythmologie et Modélisation Cardiaque LIRYC, Université de Bordeaux, Pessac, France; Inserm U1045 CRCTB, Université de Bordeaux, Bordeaux, France.

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.

No MeSH data available.


Related in: MedlinePlus