Cardiac forces regulate zebrafish heart valve delamination by modulating Nfat signaling

In the clinic, most cases of congenital heart valve defects are thought to arise through errors that occur after the endothelial–mesenchymal transition (EndoMT) stage of valve development. Although mechanical forces caused by heartbeat are essential modulators of cardiovascular development, their role in these later developmental events is poorly understood. To address this question, we used the zebrafish superior atrioventricular valve (AV) as a model. We found that cellularized cushions of the superior atrioventricular canal (AVC) morph into valve leaflets via mesenchymal–endothelial transition (MEndoT) and tissue sheet delamination. Defects in delamination result in thickened, hyperplastic valves, and reduced heart function. Mechanical, chemical, and genetic perturbation of cardiac forces showed that mechanical stimuli are important regulators of valve delamination. Mechanistically, we show that forces modulate Nfatc activity to control delamination. Together, our results establish the cellular and molecular signature of cardiac valve delamination in vivo and demonstrate the continuous regulatory role of mechanical forces and blood flow during valve formation.

Gene Expression in Proliferative Diabetic Retinopathy Using RNA-Seq Data: A Computational Study on Saudi Patients

Proliferative diabetic retinopathy is the widespread type of DM which causes chronic as well as progressive alterations at microvascular level, which particularly effects the eye. The main characteristic of this disease is the development of few new blood vessels around the retina of eye as well as at the posterior region of eye segments. For our computational analysis 155 differentially expressed genes calculated through paired t test statistics analysis using the GenePattern platform, of proliferative diabetic retinopathy in Saudi patients were downloaded. Among the 155 genes, 95 were upregulated, and 60 were downregulated. The Annotation Cluster (FAC) tool in the (DAVID) (http://david.abcc.ncifcrf.gov/home.jsp) was used to identify biological processes that are abundant in proliferative diabetic retinopathy (PDR). The functions required for response to mRNA splicing, intracellular protein transport, mRNA processing, microtubule cytoskeleton structure, and atrioventricular canal formation are represented by the GO keywords that are abundant in genes. We used the KAAS web server to identify the biological pathways of these DEGs in addition to DAVID functional analysis and found that the majority of the DEGs were associated with important biological processes, with many being classified in metabolic pathways, Spliceosome, Cell cycle, or being involved in the mRNA surveillance pathway. findings are consistent with those of earlier research. To corroborate the predictions stated in this work, which will demonstrate the role enhanced functional processes, experimental validation will be necessary.

Inferior Extensions of the Atrioventricular Node

The pathways for excitation of the atrioventricular node enter either superiorly, as the so-called ‘fast’ pathway, or inferiorly as the ‘slow’ pathway. However, knowledge of the specific anatomical details of these pathways is limited. Most of the experimental studies that established the existence of these pathways were conducted in mammalian hearts, which have subtle differences to human hearts. In this review, the authors summarise their recent experiences investigating human cardiac development, correlating these results with the arrangement of the connections between the atrial myocardium and the compact atrioventricular node as revealed by serial sectioning of adult human hearts. They discuss the contributions made from the atrioventricular canal myocardium, as opposed to the primary ring. Both these rings are incorporated into the atrial vestibules, albeit with the primary ring contributing only to the tricuspid vestibule. The atrial septal cardiomyocytes are relatively late contributors to the nodal inputs. Finally, they relate our findings of human cardiac development to the postnatal arrangement.

Common Arterial Trunk Associated with Functionally Univentricular Heart: Anatomical Study and Review of the Literature

Common arterial trunk (CAT) is a rare congenital heart disease that is commonly included into the spectrum of conotruncal heart defects. CAT is rarely associated with functionally univentricular hearts, and only few cases have been described so far. Here, we describe the anatomical characteristics of CAT associated with a univentricular heart diagnosed in children and fetuses referred to our institution, and we completed the anatomical description of this rare condition through an extensive review of the literature. The complete cohort ultimately gathered 32 cases described in the literature completed by seven cases from our unit (seven fetuses and one child). Four types of univentricular hearts associated with CAT were observed: tricuspid atresia or hypoplastic right ventricle in 16 cases, mitral atresia or hypoplastic left ventricle in 12 cases, double-inlet left ventricle in 2 cases, and unbalanced atrioventricular septal defect in 9 cases. Our study questions the diagnosis of CAT as the exclusive consequence of an anomaly of the wedging process, following the convergence between the embryonic atrioventricular canal and the common outflow tract. We confirm that some forms of CAT can be considered to be due to an arrest of cardiac development at the stages preceding the convergence.

Hypoplastic Left Heart Syndrome: Diagnostic Difficulties in Prenatal Period

The article discusses the possible diagnostic errors in the hypoplastic left heart syndrome (HLHS) with mitral atresia and intact interventricular septum. “Atrioventricular canal defects” can be commonly and mistakenly diagnosed the prenatal period in such cases. The aspects and possibilities of differential diagnosis of these defects in the prenatal period are discussed. Ultrasound sign is presented in the article, we have named it “hockey stick with puck” that characterizes the retrograde blood flow in the aortic arch. This sign is diagnosed by color Doppler mapping of the sagittal section of the ductus arteriosus and can serve as a marker of mitral/aortic atresia.

A surgical approach of an unusual variant of complete atrioventricular defect; A case report

Background Complete atrioventricular canal is a congenital heart defect that is characterized by an atrial septal defect, ventricular septal defect, and a common atrioventricular valve. Standard surgical techniques for repairing complete atrioventricular canal defect mainly includes repairing the defect with a single patch, a double patch, or with the modified single patch technique. Case presentation This paper presents a novel surgical repair technique of an unusual anatomical presentation for a complete atrioventricular canal defect in a patient with Down syndrome. Conclusions Unusual anatomical variant for congenital heart defects occurs frequently, which gives surgeons real opportunities to innovate surgical approaches. This patient was an example of an unusual anatomical presentation for complete atrioventricular canal, and the surgical technique used for this patient was novel. Follow up for these patients is mandatory for long term results.

Antenatal Diagnosis of a Partial Atrioventricular Canal with Ebstein’s Anomaly

The simultaneous occurrence of an atrioventricular canal defect (AVCD) and Ebstein’s anomaly is extremely rare, occurring in less than 0.5% of all patients with AVCD. Only 22 cases are described in the literature. This patient’s antenatal diagnosis of both Ebstein’s anomaly and partial AVCD was made at 25 weeks of gestation. The delivery was organized in a tertiary center. The initial neonatal course was difficult but with adequate treatment, a rapid improvement allowed for a gap of almost 2 years before a complete surgical repair including a cone tricuspid plasty. To our knowledge, this is the first case of antenatal diagnosis, with carefully tailored delivery, neonatal care and subsequent follow-up before indication for successful surgery.

PRC1 Stabilizes Cardiac Contraction by Regulating Cardiac Sarcomere Assembly and Cardiac Conduction System Construction

Cardiac development is a complex process that is strictly controlled by various factors, including PcG protein complexes. Several studies have reported the critical role of PRC2 in cardiogenesis. However, little is known about the regulation mechanism of PRC1 in embryonic heart development. To gain more insight into the mechanistic role of PRC1 in cardiogenesis, we generated a PRC1 loss-of-function zebrafish line by using the CRISPR/Cas9 system targeting rnf2, a gene encoding the core subunit shared by all PRC1 subfamilies. Our results revealed that Rnf2 is not involved in cardiomyocyte differentiation and heart tube formation, but that it is crucial to maintaining regular cardiac contraction. Further analysis suggested that Rnf2 loss-of-function disrupted cardiac sarcomere assembly through the ectopic activation of non-cardiac sarcomere genes in the developing heart. Meanwhile, Rnf2 deficiency disrupts the construction of the atrioventricular canal and the sinoatrial node by modulating the expression of bmp4 and other atrioventricular canal marker genes, leading to an impaired cardiac conduction system. The disorganized cardiac sarcomere and defective cardiac conduction system together contribute to defective cardiac contraction. Our results emphasize the critical role of PRC1 in the cardiac development.

EFFECTIVE CORRECTION OF THE COMMON ATRIOVENTRICULAR CANAL WITH TETRALOGY OF FALLOT AND HYPOPLASIA OF THE RIGHT VENTRICLE IN A CHILD

The paper presents a description of a case of successful one and a half ventricular correction of a complex congenital cardiac anomalies, including the common atrioventricular canal, tetralogy of Fallot, and hypoplasia of the right ventricle in a child (2 year and 4 months). Ararecongenitalanomalycharacterized by acombinationof intracardiac defects, required an innovative surgical approach, the exclusivity of this clinical case has determined. The surgical strategy of complete atrioventricular canal defect is determined by a number of factors. One of the most important is balance between right and left ventricular outputs. The balanced type with adequate development of the ventricles involves the biventricular repair performance. Unbalancedatrioventricular canal defects includea hypoplastic ventricle. Reconstructive surgeryfor onehypoplasticventricle is oriented towards the degree of hypoplasia. In particular, a mild right ventricular hypoplasia allows perfoming biventricular radical operation while a severe degree suggests univentricular repair. In case of borderline, moderate degree of hypoplastic right ventricle the one and half ventricle repair can be carried out. Another important point is the presence of concomitant pulmonic stenosis required the choice of optimal method and material for reconstruction which is not always obvious and often it is the subject of debates. This report presents a description of the diagnostic stages with an emphasis on determining the type of balance of the common atrioventricular canal, the degree of hypoplasia of the right ventricle, the approach to choosing the optimal method for correcting the defect in general and the material for reconstructing the outflow pathway from the right ventricle in particular, as well as the subsequent successful correction of congenital multicomponent cardiac abnormalities in a young patient.

Copy number variation analysis in Chinese children with complete atrioventricular canal and single ventricle

Background Congenital heart disease (CHD) is one of the most common birth defects. Copy number variations (CNVs) have been proved to be important genetic factors that contribute to CHD. Here we screened genome-wide CNVs in Chinese children with complete atrioventricular canal (CAVC) and single ventricle (SV), since there were scarce researches dedicated to these two types of CHD. Methods We screened CNVs in 262 sporadic CAVC cases and 259 sporadic SV cases respectively, using a customized SNP array. The detected CNVs were annotated and filtered using available databases. Results Among 262 CAVC patients, we identified 6 potentially-causative CNVs in 43 individuals (16.41%, 43/262), including 2 syndrome-related CNVs (7q11.23 and 8q24.3 deletion). Surprisingly, 90.70% CAVC patients with detected CNVs (39/43) were found to carry duplications of 21q11.2–21q22.3, which were recognized as trisomy 21 (Down syndrome, DS). In CAVC with DS patients, the female to male ratio was 1.6:1.0 (24:15), and the rate of pulmonary hypertension (PH) was 41.03% (16/39). Additionally, 6 potentially-causative CNVs were identified in the SV patients (2.32%, 6/259), and none of them was trisomy 21. Most CNVs identified in our cohort were classified as rare (< 1%), occurring just once among CAVC or SV individuals except the 21q11.2–21q22.3 duplication (14.89%) in CAVC cohort. Conclusions Our study identified 12 potentially-causative CNVs in 262 CAVC and 259 SV patients, representing the largest cohort of these two CHD types in Chinese population. The results provided strong correlation between CAVC and DS, which also showed sex difference and high incidence of PH. The presence of potentially-causative CNVs suggests the etiology of complex CHD is incredibly diverse, and CHD candidate genes remain to be discovered.