Comparative transcriptome analysis of atrial septal defect identifies dysregulated genes during heart septum morphogenesis

Trends in Congenital Heart Disease

“…[30][31][32] Transcriptome analyses of discarded CHD tissues may disclose transcriptional changes that accompany abnormal hemodynamic load and define posttranscriptional RNA processing that regulates cardiac development. [33][34][35][36][37] We can expect the future to bring the identification of new classes of CHD mutations and novel insights into the pathways that these mutations impact and a better understanding of genes that modify the responses to hemodynamic and environmental stress, as well. Because the number of causative variants is large and the frequency of causative variants for individual genes is low, sufficiently sizeable cohorts of probands and parents must be assembled across multiple centers, as is currently achieved in the NHLBI Pediatric Cardiac Genomics Consortium.…”

MicroRNA profiling of patients with sporadic atrial septal defect

“…According to the parallel stages of heart development in mice and humans, atrial septum formation starts at 7.5 weeks in humans and at E11.5 days in mice [37]. Based on this comparison, we determined that a human gestational age of 30-33 weeks is parallel to mouse embryonic stages beyond E17.5, as we have previously reported [38]. In the upregulated cluster, miR-29b-3p showed stable expression and miR-29c-3p was downregulated during the heart development process (Figure 4(a)), allowing us to exclude differences caused by developmental stages.…”

Transcriptome analysis defines myocardium gene signatures in children with ToF and ASD and reveals disease-specific molecular reprogramming in response to surgery with cardiopulmonary bypass

“…In the last years, several studies have demonstrated the value of myocardium transcriptome analysis for elucidating the molecular mechanisms underlying cardiovascular disease pathogenesis and identifying novel biomarkers for prognostic and therapeutic purposes [10,[13][14][15][16][17]30]. In this study, we carry out the first comparative gene expression profiling of ToF and ASD right atrial specimens before and after surgery with CPB.…”

“…Another significant difference between ToF and ASD transcriptomes was related to the enrichment of sarcomeric protein-coding genes in ASD atrial samples. Although only MYL3 dysregulation has been previously linked to ASD pathogenesis [16], ACTA1 and MURC overexpression was reported to contribute to cardiac contractile dysfunction and conduction disturbances in mouse models [44,45], whereas MYL3, MURC, and MYH11 gene mutations or copy number variants were found associated with cardiomyopathy or CHDs [46][47][48]. Based on this evidence, we hypothesize that the observed upregulation of contractile fiber genes in the ASD myocardium and functional interactions among their products, predicted by network analysis, are critical for disease development.…”

“…Although significant advances in the clinical management of ToF and ASD patients have been made in the last few decades, much remains to be elucidated regarding the molecular mechanisms underlying disease pathogenesis and myocardial response to corrective surgery with CPB. In the field of cardiomyopathy, microarraybased gene expression profiling has become an important approach for the characterization of the molecular bases of disease pathogenesis, progression, and response to surgery/therapy, contributing to the identification of Page 3 of 20 Raggi et al J Transl Med (2020) 18:21 novel biomarkers essential for the refinement of patient diagnostic and prognostic evaluation and the design of tailored treatment strategies [10,[13][14][15][16][17].…”