Tetralogy of fallot as a model to study cardiac progenitor cell migration and differentiation during heart development.
Tetralogy of Fallot (ToF) has long been considered a congenital disorder that occurs due to environmental alterations during gestation. Recently, several mutated genes have been discovered that are thought to be responsible for the malformations observed in ToF. These genetic mutations, which are microdeletions, are sporadic and are frequently also present in trisomy 21 patients. The ToF malformations can be lethal, but for the last 50 years, surgical repairs that place an artificial patch to repair the four features of ToF have improved the survival of patients with ToF. However, 0.5% to 6% of patients who survive after surgical repair of ToF die of sudden cardiac death caused by ventricular tachycardia. In fact, even if the septum has been repaired, the patch used to close the interventricular defect may cause deformation of the heart, altering the force lines essential for normal function of the right ventricle. In the present review, we hypothesize that mutations in the GATA binding protein 4 (GATA-4)/friend of GATA-2 transcriptional complex and NKX2.5 gene may play a role in the abnormal migration and behavior of precardiac cells during heart development in patients with ToF. An understanding of cardiac precursor cell behavior is needed in order for future research regarding therapeutic approaches to correct the defects seen in ToF without affecting cardiac hemodynamics to be successful.
Di Felice
Valentina
V
Dipartimento di Medicina Sperimentale, Università degli studi di Palermo, Italy. vdfelice@inwind.it
Zummo
Giovanni
G
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D050991:GATA4 Transcription Factor / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009154:Mutation; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D038081:Organogenesis / Q000235:genetics; D013234:Stem Cells / Q000473:pathology*; D013771:Tetralogy of Fallot / Q000235:genetics / Q000473:pathology* / Q000601:surgery; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D050991:GATA4 Transcription Factor; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; C095552:NKX2-5 protein, human; D014157:Transcription Factors