Congenital Heart Diseases and Biotechnology: Connecting by Connexin

2014 ◽  
Vol 995 ◽  
pp. 85-112
Author(s):  
Naznin Sultana ◽  
Nobuhiro Nakamura ◽  
Shigehisa Hirose ◽  
Koichi Kutsuzawa ◽  
Toshihiro Akaike ◽  
...  
Keyword(s):  
Gap Junction ◽  
Heart Development ◽  
Congenital Heart ◽  
Cellular Proliferation ◽  
Cardiac Tissue ◽  
Heart Diseases ◽  
Heart Defects ◽  
Normal Function ◽  
Congenital Heart Diseases ◽  
Developmental Defects

Heart development is a precisely harmonized process of cellular proliferation, migration, differentiation, and integrated morphogenetic interactions, and therefore it is extremely vulnerable to developmental defects that cause congenital heart diseases (CHD). One of the major causes of CHD has been shown to be the mutations in key cardiac channel-forming proteins namely, connexins (Cxs). Cxs are tetra-spanning transmembrane proteins that form gap junction channels and hemichannels on cellular membrane. They allow passage of small molecules or ions between adjacent cells or between cells and the extracellular environment. Studies have revealed that the spatiotemporal expression of Cxs mainly, Cx31.9, Cx40, Cx43, and Cx45 is essentially involved in early developmental events, morphogenetic transformations, maturation, and functional significance of heart. Our lab and others have shown that mutations in gap junction proteins could result in impaired trafficking, misfolding, and improper channel function of these proteins. It has also been shown that differential expressions of cardiac Cxs are associated with pathophysiological conditions of heart. Collectively, these conditions are coupled with abrogated or modified functionality of relevant channels in cardiac tissue, which are associated with many pathological situations, including CHD. Since CHD are a major cause of morbidity, therefore recovery of such kind of heart defects associated with Cxs is extremely important but remains highly challenging. In this review, we will summarize the role of Cxs in development, morphogenesis, maturation, normal function, and pathology of heart, and propose possible bioengineering techniques to recover defects in cardiac tissues related to the modified functions of Cxs.

scholarly journals Epigenetic Regulation of Cardiac Neural Crest Cells

2021 ◽  
Vol 9 ◽  
Author(s):  
Shun Yan ◽  
Jin Lu ◽  
Kai Jiao
Keyword(s):  
Neural Crest ◽  
Epigenetic Regulation ◽  
Heart Development ◽  
Congenital Heart ◽  
Heart Diseases ◽  
Heart Defects ◽  
Neural Crest Cells ◽  
Abnormal Development ◽  
Cardiac Neural Crest ◽  
Epigenetic Regulators

The cardiac neural crest cells (cNCCs) is a transient, migratory cell population that contribute to the formation of major arteries and the septa and valves of the heart. Abnormal development of cNCCs leads to a spectrum of congenital heart defects that mainly affect the outflow region of the hearts. Signaling molecules and transcription factors are the best studied regulatory events controlling cNCC development. In recent years, however, accumulated evidence supports that epigenetic regulation also plays an important role in cNCC development. Here, we summarize the functions of epigenetic regulators during cNCC development as well as cNCC related cardiovascular defects. These factors include ATP-dependent chromatin remodeling factors, histone modifiers and DNA methylation modulators. In many cases, mutations in the genes encoding these factors are known to cause inborn heart diseases. A better understanding of epigenetic regulators, their activities and their roles during heart development will ultimately contribute to the development of new clinical applications for patients with congenital heart disease.

Fetal echocardiography in Lithuania: traditions, significance and problems

2010 ◽  
Vol 17 (3-4) ◽  
pp. 116-122
Author(s):  
Ramunė VANKEVIČIENĖ
Keyword(s):  
Congenital Heart Defects ◽  
Congenital Heart ◽  
Heart Diseases ◽  
Fetal Echocardiography ◽  
Heart Defects ◽  
Tertiary Care ◽  
Congenital Heart Diseases ◽  
Conduction Disturbances ◽  
Tertiary Care Centers ◽  
Almost All

Background. The discovery of ultrasound has made a revolution in almost all fields of medicine. The past three decades have withessed an intensive development of fetal echocardiography methods and technique. The aim of the paper is to present a review of the results and trends of the last 10 years of fetal echocardiography in Lithuania and to show the spectrum and outcomes of prenatally detected congenital heart diseases. Materials and methods. Fetal echocardiography was performed for 1816 fetuses during the period from 1999 to 2009. Results. Cardiac pathology was diagnosed in 176 (9.7%) fetuses. Heart defects were detected in 112 (63.6%) of them, cardiac rhythm and conduction disturbances in 62 (35.2%), cardiomyopathy in 2 (1.1%) fetuses, and heart rhabdomyoma in 1 (0.6%) fetus. The general rate of the postnatal diagnosis of congenital heart defects in Lithuania was about 10%. Most of fetal cardiac diseases (70.5%) were diagnosed after 22 weeks of gestation. Because most of antenatally diagnosed congenital heart defects (74%) were critical and inconsistent with life, a large part of newborns (40.2%) died in the neonatal period, 10.7% of fetuses died in utero, and 8% of pregnancies were terminated by abortion. The data demonstrate good tendencies: the diagnosis has become earlier, a wider spectrum of diseases have been diagnosed, more newborns have survived. Our survey shows that 41.1% of newborns with prenatally diagnosed congenital heart defects have survived. Conclusions. 10% of severe congenital heart diseases are detected prenatally in Lithuania. The efficacy of antenatal diagnostics depends on the qualification of specialists, the number of tertiary care centers, on a successful collaboration among pediatric cardiologists, obstetricians and geneticists. The main problem is an insufficient preparation of obstetricians, the uncertified favor of pediatric cardiologist. Keywords: congenital heart disease, fetal echocardiography, antenatal diagnostics

scholarly journals Result of airway reconstruction by slide tracheobronchoplasty in children with congenital heart diseases and severe airway stenosis at Hanoi Heart Hospital: A series case report

2021 ◽  
Vol 35 ◽  
pp. 67-74
Author(s):  
Tong Duy Phuc ◽  
Nguyen Sinh Hien ◽  
Nguyen Dang Hung ◽  
Vuong Hoang Dung
Keyword(s):  
Congenital Heart ◽  
Heart Diseases ◽  
Heart Defects ◽  
Case Series ◽  
Congenital Heart Diseases ◽  
Tracheobronchial Stenosis ◽  
Airway Stenosis ◽  
Heart Repair ◽  
Airway Reconstruction ◽  
Heart Hospital

Abstract: Congenital airway stenosis (tracheobronchial stenosis) in children is rare, difficult to treat and become more complex when associated with congenital heart defects. In severe airway stenosis, slide tracheobronchoplasty is the most optimal strategy to manage this condition, yet really challenging. We report case series with this combined condition of airway stenosis and congenital heart diseases, which were successfully treated by slide tracheobronchoplasty with concomitant heart repair. We also discuss about the indication, surgical technique as well as postoperative care.

scholarly journals Genetic study in congenital heart defects

2019 ◽  
Vol 7 (5) ◽  
pp. 1696
Author(s):  
Syed Abir Hussain ◽  
Nasir U din Wani ◽  
Tasneem Muzaffar ◽  
Abdul Majeed Dar ◽  
Mohammad Akbar Bhat ◽  
...  
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Congenital Heart ◽  
Cardiac Tissue ◽  
Sex Chromosome ◽  
Heart Diseases ◽  
Heart Defects ◽  
Sex Linkage ◽  
Mutation Site

Background: Congenital heart diseases (CHD) are relatively common with a prevalence ranging from 3.7 to 17.5 per 1000 live births. Little is known about genetic link with respect to congenital heart disease. Iroquoise (Irx) homeobox genes have been widely studied and their expression in both developing and adult heart. Author tried to study the role of irx4 and irx5 genes in structural congenital heart disease, keeping the focus on study reported by Cheng Z et al.Methods: Author studied reported mutation site sequences in 25 various congenital heart disease patients and control healthy relatives of patients. It is a unique study and there has not been such a study reported in literature till date. Besides comparison with healthy related controls, author took cardiac tissue biopsy in patients while doing corrective cardiac surgery. However, blood samples were taken from controls due to ease of feasibility.Results: Although, there were no sequence variations in the studied exon regions, but author got a base pair sequence change at 6 bp intron region, which is near the exon splice site in irx4 gene. Besides two ASD patient’s male children (one child each) had ASD prompting us to believe some role of sex linkage. However later needs pedigree analysis and sex chromosome studies for further analysis.Conclusions: Gene sequence in the Kashmiri population is unique. There is possibility of role of irx genes in CHD. ASD might have sex linkage in some.

scholarly journals A cis-regulatory-directed pipeline for the identification of genes involved in cardiac development and disease

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Hieu T. Nim ◽  
Louis Dang ◽  
Harshini Thiyagarajah ◽  
Daniel Bakopoulos ◽  
Michael See ◽  
...  
Keyword(s):  
Heart Development ◽  
Congenital Heart ◽  
Cardiac Tissue ◽  
Cardiac Development ◽  
Heart Diseases ◽  
Regulatory Element ◽  
Adult Mortality ◽  
Disease Genes ◽  
Novel Genes ◽  
Specific Expression

Abstract Background Congenital heart diseases are the major cause of death in newborns, but the genetic etiology of this developmental disorder is not fully known. The conventional approach to identify the disease-causing genes focuses on screening genes that display heart-specific expression during development. However, this approach would have discounted genes that are expressed widely in other tissues but may play critical roles in heart development. Results We report an efficient pipeline of genome-wide gene discovery based on the identification of a cardiac-specific cis-regulatory element signature that points to candidate genes involved in heart development and congenital heart disease. With this pipeline, we retrieve 76% of the known cardiac developmental genes and predict 35 novel genes that previously had no known connectivity to heart development. Functional validation of these novel cardiac genes by RNAi-mediated knockdown of the conserved orthologs in Drosophila cardiac tissue reveals that disrupting the activity of 71% of these genes leads to adult mortality. Among these genes, RpL14, RpS24, and Rpn8 are associated with heart phenotypes. Conclusions Our pipeline has enabled the discovery of novel genes with roles in heart development. This workflow, which relies on screening for non-coding cis-regulatory signatures, is amenable for identifying developmental and disease genes for an organ without constraining to genes that are expressed exclusively in the organ of interest.

scholarly journals Nonmedical Determinants of Congenital Heart Diseases in Children from the Perspective of Mothers: A Qualitative Study in Iran

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Maryam Borjali ◽  
Mostafa Amini-Rarani ◽  
Mehdi Nosratabadi
Keyword(s):  
Qualitative Study ◽  
Congenital Heart ◽  
Heart Diseases ◽  
Heart Defects ◽  
Well Being ◽  
Noncommunicable Diseases ◽  
Congenital Heart Diseases ◽  
Semistructured Interview ◽  
Congenital Diseases ◽  
The World

Introduction. Mortality due to noncommunicable diseases has increased in the world today with the advent of demographic shifts, growing age, and lifestyle patterns in the world, which have been affected by economic and social crises. Congenital heart defects are one of the forms of diseases that have raised infant mortality worldwide. The objective of present study was to identify nonmedical determinants related to this abnormality from the mother’s perspectives. Methods. This research was a qualitative study and the data collection method was a semistructured interview with mothers who had children with congenital heart diseases referring to the Shahid Rajaei Heart Hospital in Tehran, Iran. A thematic analysis approach was employed to analyze transcribed documents assisted by MAXQDA Plus version 12. Results. Four general themes and ten subthemes including social contexts (social harms, social interactions, and social necessities), psychological contexts (mood disorders and mental well-being), cultural contexts (unhealthy lifestyle, family culture, and poor parental health behaviors), and environmental contexts (living area and polluted air) were extracted from interviews with mothers of children with congenital heart diseases. Conclusions. Results suggest that factors such as childhood poverty, lack of parental awareness of congenital diseases, lack of proper nutrition and health facilities, education, and lack of medical supervision during pregnancy were most related with the birth of children with congenital heart disease from mothers’ prospective. In this regard, targeted and intersectorial collaborations are proposed to address nonmedical determinants related to the incidence of congenital heart diseases.

scholarly journals Analysis of the interconnection of the GSTP1, CYP1A2, CYP1A1 genes in children with congenital heart diseases

2020 ◽  
Vol 65 (3) ◽  
pp. 39-43
Author(s):  
A. V. Tsepokina ◽  
A. V. Ponasenko ◽  
A. V. Shabaldin
Keyword(s):  
Congenital Heart ◽  
Heart Diseases ◽  
Heart Defects ◽  
Congenital Heart Diseases ◽  
Genotype Distribution ◽  
Healthy Children ◽  
Rt Pcr ◽  
Locus Model ◽  
Healthy Donors ◽  
Pcr Method

The article presents data on the study of gene interconnections between the xenobiotics detoxification genes in various phases.Materials and methods. The study involves 131 children with congenital heart diseases (CHD) and 103 conditionally healthy children. The genotyping was performed by RT-PCR method using TaqMan probes. Intergenic bonds were analyzed via MDR v.3.0.2.Results and conclusion. We discovered no statistically significant differences in the genotype distribution in children with CHD and conditionally healthy donors. The analysis of intergenic interactions helped to develop a five-locus model characterized by the highest reproducibility, sensitivity and specificity: GSTP1 rs1793068 – GSTP1 rs6591256 – GSTP1 rs1871042 – CYP1A1 rs1048943 – CYP1A2 rs762551. This model was used to determine a number of protective and risky combinations of congenital heart defects-associated genotypes in children.

Traffic Jam Response

2015 ◽  
Vol 77 (8) ◽  
pp. 632-636
Author(s):  
Robert M. Kao
Keyword(s):  
Heart Development ◽  
Congenital Heart ◽  
Heart Diseases ◽  
Pulmonary Artery Stenosis ◽  
Congenital Heart Diseases ◽  
Genetic Aberrations ◽  
Traffic Jam ◽  
Morphological Complexity ◽  
Hands On ◽  
Students First

Congenital heart disease in newborns exhibits a spectrum of defects, one of which is the occlusion of the vascular conduits of the arteries. For students first learning about cardiovascular lesions, the tortuous path of blood vessels can be visually overwhelming to the untrained eye, and useful models are needed to help deconstruct the morphological complexity of heart chambers and vessel location during heart development and disease. Here, I present two hands-on activities to explore how pulmonary artery stenosis may have dire consequences, such as cardiac muscle cell hypertrophy. These activities will not only help students explore genetic aberrations associated with congenital heart diseases, but will also encourage them to think about how to develop molecular and cellular strategies that fix primary obstruction in other branched organs such as the gut, kidney, and pancreas.

scholarly journals HOTAIR Is a Potential Novel Biomarker in Patients with Congenital Heart Diseases

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Yu Jiang ◽  
Hongdan Mo ◽  
Jing Luo ◽  
Suhong Zhao ◽  
Shuang Liang ◽  
...  
Keyword(s):  
Heart Development ◽  
Congenital Heart ◽  
Heart Diseases ◽  
Right Atrial ◽  
Control Group ◽  
Congenital Heart Diseases ◽  
Cardiac Tissues ◽  
Polycomb Repressive Complex 2 ◽  
Valvular Heart Diseases ◽  
Right Atrial Appendage

Objective. To investigate the expression of HOX transcript antisense RNA (HOTAIR) in cardiac tissues and plasma of patients with congenital heart diseases (CHDs). Methods. qRT-PCR was used to detect the expression of HOTAIR in right atrial appendage tissues of 16 patients with CHDs and 14 patients with rheumatic valvular heart diseases (RVHDs), as well as in plasma of 36 normal people and 90 patients with CHDs including 36 cases of ASD, 23 cases of VSD, and 31 cases of PDA. Besides, the proteins interacting with HOTAIR were obtained from databases. Results. The HOTAIR expression in cardiac tissues of CHDs group was significantly higher than that of the RVHDs group (P<0.01). Compared with the control group, the expression of plasma HOTAIR in the ASD group, the VSD group, and the PDA group was all remarkably upregulated (P<0.01), whereas there was no relationship between HOTAIR and pulmonary arterial hypertension and defects size. Databases show that HOTAIR is associated with polycomb repressive complex 2 (PRC2) which contributes to heart development. Conclusion. The levels of HOTAIR were increased in cardiac tissues and plasma of patients with CHDs. HOTAIR is a potential novel diagnostic biomarker in patients with CHDs.

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