ABSTRACT
Congenital heart disease (CHD) is the leading cause of death in infants in the world. The study of CHDs has come a long way since their classification and description. Although transcriptional programmes that are impaired in individuals with CHDs are being identified, the mechanisms of how these deficiencies translate to a structural defect are unknown. In this study, using high-throughput microarray analysis and molecular network analysis, FXN was identified to be the most differentially expressed key gene in CHD. By TargetScan analysis, we predicted FXN was the target gene of miRNA-145 and miRNA-182. Through real-time PCR analysis of clinical samples and experiments in cell lines, we confirmed that miRNA-145 but not miRNA-182 directly binds to the 3' UTR region of FXN and negatively regulates its expression. We further found that through targeting FXN, miRNA-145 regulates apoptosis and mitochondrial function. In general, our study confirmed the differentially expressed FXN regulates the development of CHD and the differential expression was under the control of miRNA-145. These results might provide new insight into the understanding of the CHD pathogenesis and may facilitate further therapeutic studies.
Subject(s)
3' Untranslated Regions/genetics , Heart Defects, Congenital/genetics , Iron-Binding Proteins/genetics , MicroRNAs/genetics , Case-Control Studies , Child , Child, Preschool , China , Female , Gene Regulatory Networks , Humans , Male , Microarray Analysis , FrataxinABSTRACT
BACKGROUND: Perimembranous ventricular septal defects (pmVSDs) are one of the most common forms of congenital cardiac malformation in children. Results of transcatheter pmVSD closure remain debatable, prompting the need for further evaluation with regard to the safety and efficacy of this procedure. The aim of the study was to analyze the safety, efficacy, and long-term follow-up data associated with transcatheter closure of pmVSDs in children using symmetric occluders. METHODS: From December 2002 to October 2011, 525 children with pmVSDs between 2 and 12 years of age underwent transcatheter closure at three major heart centers in northwest China with symmetric pmVSD occluders. All patients were followed up until October 2011 with electrocardiogram and transthoracic echocardiography. Adverse events were recorded and evaluated. RESULTS: There were 252 male and 273 female patients with an average weight of 21.5 kg. The mean age at the time of transcatheter closure was 5.6 years, and the average ratio of pulmonic to systemic blood flow was 2.5. Transcatheter intervention was successfully performed in 502 patients (95.6%). The median device size implanted was 6.5 mm (range, 4 to 18 mm). During a median 45-month follow-up period, no mortality occurred. A total of three major adverse events (0.6%) were reported; two were valve-related. Meanwhile, 104 minor adverse events were detected during the entire follow-up period. All individuals experiencing major adverse events were younger than 3 years of age. The incidence of major adverse events in patients younger than 3 years old was significantly higher than that of patients older than 3 years old (3.75% versus 0.00%; Fisher's exact test p=0.004). CONCLUSIONS: Data from the current study suggest that transcatheter pmVSD closure using symmetric occluders displayed an excellent success rate and long-term follow-up results. The transcatheter approach provides a less-invasive alternative to open surgery and displays some promise in the treatment of pmVSDs in certain patient populations.
