scholarly journals Mechanosensitive Pathways in Heart Development: Findings from Chick Embryo Studies

2021 ◽  
Vol 8 (4) ◽  
pp. 32
Author(s):  
Maha Alser ◽  
Samar Shurbaji ◽  
Huseyin C. Yalcin
Keyword(s):  
Chick Embryo ◽  
Heart Development ◽  
Congenital Heart ◽  
Morphological Changes ◽  
Heart Defects ◽  
Genetic Regulation ◽  
The Body ◽  
Embryonic Chick ◽  
Chemical Treatments ◽  
Developing Heart

The heart is the first organ that starts to function in a developing embryo. It continues to undergo dramatic morphological changes while pumping blood to the rest of the body. Genetic regulation of heart development is partly governed by hemodynamics. Chick embryo is a major animal model that has been used extensively in cardiogenesis research. To reveal mechanosensitive pathways, a variety of surgical interferences and chemical treatments can be applied to the chick embryo to manipulate the blood flow. Such manipulations alter expressions of mechanosensitive genes which may anticipate induction of morphological changes in the developing heart. This paper aims to present different approaches for generating clinically relevant disturbed hemodynamics conditions using this embryonic chick model and to summarize identified mechanosensitive genes using the model, providing insights into embryonic origins of congenital heart defects.

scholarly journals Altered Inflow Hemodynamics affects Heart Development in a Side Specific Manner in the Embryonic Heart

2020 ◽  
Author(s):  
Maha W Alser ◽  
Huseyin Enes Salman ◽  
Huseyin Cagatay Yalcin
Keyword(s):  
Chick Embryo ◽  
Congenital Heart Defects ◽  
Heart Development ◽  
Congenital Heart ◽  
Heart Defects ◽  
Embryonic Heart ◽  
Cfd Analysis ◽  
Micro Ct ◽  
Left Heart ◽  
Right Heart

Background: Hemodynamics, forces from the flowing blood in the heart, is a major epigenetic factor for heart development. Disturbed hemodynamics were shown to induce cardiac malformations in the embryonic heart. Clinically relevant congenital heart defects (CHDs) can be introduced surgically in the lab by disturbing the hemodynamics, like Hypoplastic left heart syndrome (HLHS), characterized by underdeveloped left ventricle is underdeveloped. Left atrial ligation (LAL) on chick embryo is an experimental technique to produce a HLHS-like phenotype. Aims: To reveal mechanobiological mechanisms associated with disturbed hemodynamics that influence the progression of left ventricular hypoplasia using chick embryo model. We also introduce a new technique which we called right atrial ligation (RAL), to examine effect of flow disturbance in right heart. Methods: We combined multiple novel techniques in this research: Heart function was assessed via Echocardiography. Computational fluid dynamics (CFD) analysis was adapted for detailed hemodynamics assessment, such as wall shear stress and blood flow patterns. Heart morphology was assessed by histology, and micro-CT. Results: Echocardiography and CFD analysis showed flow and WSS levels decreased for the flow constricted side resulting in the flow diversion to the opposite side: LAL diverted flow to right side and RAL to left side. This disturbance resulted in underdevelopment of left heart (valve and ventricle) in LAL and underdevelopment of right heart in RAL, revealed with histology and micro-CT. Left side was affected more compared to right side, demonstrating higher plasticity in left heart. Conclusion: This study indicates the critical importance of altered inflow hemodynamics in cardiac development specifically valve and ventricle development. Our comprehensive approach can be used to predict the initiation and growth of congenital heart defects.

scholarly journals The developing heart: from The Wizard of Oz to congenital heart disease

Development ◽  
2020 ◽  
Vol 147 (21) ◽  
pp. dev194233 ◽  
Author(s):  
Benoit G. Bruneau
Keyword(s):  
Developmental Biology ◽  
Congenital Heart Disease ◽  
Heart Development ◽  
Congenital Heart ◽  
Heart Defects ◽  
Lessons Learned ◽  
Postnatal Life ◽  
Wizard Of Oz ◽  
Developing Heart ◽  
New Concepts

ABSTRACTThe heart is an essential organ with a fascinating developmental biology. It is also one of the organs that is most often affected in human disease, either during development or in postnatal life. Over the last few decades, insights into the development of the heart have led to fundamental new concepts in gene regulation, but also to genetic and mechanistic insights into congenital heart defects. In more recent years, the lessons learned from studying heart development have been applied to interrogating regeneration of the diseased heart, exemplifying the importance of understanding the mechanistic underpinnings that lead to the development of an organ.

scholarly journals Abnormal Cardiac Development in the Absence of Heart Glycogen

2004 ◽  
Vol 24 (16) ◽  
pp. 7179-7187 ◽  
Author(s):  
Bartholomew A. Pederson ◽  
Hanying Chen ◽  
Jill M. Schroeder ◽  
Weinian Shou ◽  
Anna A. DePaoli-Roach ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Cardiac Muscle ◽  
Heart Development ◽  
Congenital Heart ◽  
Cardiac Development ◽  
Glycogen Synthase ◽  
Heart Defects ◽  
Mendelian Inheritance ◽  
And Function ◽  
Impaired Cardiac Function

ABSTRACT Glycogen serves as a repository of glucose in many mammalian tissues. Mice lacking this glucose reserve in muscle, heart, and several other tissues were generated by disruption of the GYS1 gene, which encodes an isoform of glycogen synthase. Crossing mice heterozygous for the GYS1 disruption resulted in a significant underrepresentation of GYS1-null mice in the offspring. Timed matings established that Mendelian inheritance was followed for up to 18.5 days postcoitum (dpc) and that ∼90% of GYS1-null animals died soon after birth due to impaired cardiac function. Defects in cardiac development began between 11.5 and 14.5 dpc. At 18.5 dpc, the hearts were significantly smaller, with reduced ventricular chamber size and enlarged atria. Consistent with impaired cardiac function, edema, pooling of blood, and hemorrhagic liver were seen. Glycogen synthase and glycogen were undetectable in cardiac muscle and skeletal muscle from the surviving null mice, and the hearts showed normal morphology and function. Congenital heart disease is one of the most common birth defects in humans, at up to 1 in 50 live births. The results provide the first direct evidence that the ability to synthesize glycogen in cardiac muscle is critical for normal heart development and hence that its impairment could be a significant contributor to congenital heart defects.

scholarly journals Focused Strategies for Defining the Genetic Architecture of Congenital Heart Defects

Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 827
Author(s):  
Lisa J. Martin ◽  
D Woodrow Benson
Keyword(s):  
Genetic Variation ◽  
Congenital Heart Defects ◽  
Heart Development ◽  
Genetic Architecture ◽  
Congenital Heart ◽  
Rare Variants ◽  
Heart Defects ◽  
Genetic Origin ◽  
Genetic Studies ◽  
The Ideal

Congenital heart defects (CHD) are malformations present at birth that occur during heart development. Increasing evidence supports a genetic origin of CHD, but in the process important challenges have been identified. This review begins with information about CHD and the importance of detailed phenotyping of study subjects. To facilitate appropriate genetic study design, we review DNA structure, genetic variation in the human genome and tools to identify the genetic variation of interest. Analytic approaches powered for both common and rare variants are assessed. While the ideal outcome of genetic studies is to identify variants that have a causal role, a more realistic goal for genetic analytics is to identify variants in specific genes that influence the occurrence of a phenotype and which provide keys to open biologic doors that inform how the genetic variants modulate heart development. It has never been truer that good genetic studies start with good planning. Continued progress in unraveling the genetic underpinnings of CHD will require multidisciplinary collaboration between geneticists, quantitative scientists, clinicians, and developmental biologists.

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.

scholarly journals Say NO to ROS: Their Roles in Embryonic Heart Development and Pathogenesis of Congenital Heart Defects in Maternal Diabetes

Antioxidants ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 436 ◽  
Author(s):  
Engineer ◽  
Saiyin ◽  
Greco ◽  
Feng
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Congenital Heart Defects ◽  
Heart Development ◽  
Congenital Heart ◽  
Heart Defects ◽  
Maternal Diabetes ◽  
Embryonic Heart ◽  
Pregestational Diabetes ◽  
Enos Uncoupling

Congenital heart defects (CHDs) are the most prevalent and serious birth defect, occurring in 1% of all live births. Pregestational maternal diabetes is a known risk factor for the development of CHDs, elevating the risk in the child by more than four-fold. As the prevalence of diabetes rapidly rises among women of childbearing age, there is a need to investigate the mechanisms and potential preventative strategies for these defects. In experimental animal models of pregestational diabetes induced-CHDs, upwards of 50% of offspring display congenital malformations of the heart, including septal, valvular, and outflow tract defects. Specifically, the imbalance of nitric oxide (NO) and reactive oxygen species (ROS) signaling is a major driver of the development of CHDs in offspring of mice with pregestational diabetes. NO from endothelial nitric oxide synthase (eNOS) is crucial to cardiogenesis, regulating various cellular and molecular processes. In fact, deficiency in eNOS results in CHDs and coronary artery malformation. Embryonic hearts from diabetic dams exhibit eNOS uncoupling and oxidative stress. Maternal treatment with sapropterin, a cofactor of eNOS, and antioxidants such as N-acetylcysteine, vitamin E, and glutathione as well as maternal exercise have been shown to improve eNOS function, reduce oxidative stress, and lower the incidence CHDs in the offspring of mice with pregestational diabetes. This review summarizes recent data on pregestational diabetes-induced CHDs, and offers insights into the important roles of NO and ROS in embryonic heart development and pathogenesis of CHDs in maternal diabetes.

Rehabilitation potential in the children after surgical correction of congenital heart defects in different age periods

10.12737/7238 ◽  
2014 ◽  
Vol 8 (1) ◽  
pp. 0-0
Author(s):  
Любчик ◽  
V. Lyubchik ◽  
Голубова ◽  
T. Golubova ◽  
Елисеева ◽  
...  
Keyword(s):  
Congenital Heart ◽  
Heart Defects ◽  
Heart Rhythm ◽  
The Body ◽  
Surgical Correction ◽  
Self Assessment ◽  
Sf 36 ◽  
Rehabilitation Potential

Comparative evaluation of rehabilitation potential in 20 girls at the sanatorium stage of rehabilitation after surgical correction of congenital heart disease in different age periods was carried out. Structural and functional diagnoses were specified to determine the level of rehabilitation potential. Identified violations were assessed as the loss or absence, reduction, addition or excess. Research methods included: clinical examination with determination of the level of physical development on the body mass index, functional orthostatic test, as-sessment of the estimated impact of blood volume and "double work", Doppler echocardiography, spectral analysis of heart rhythm, some indicators of emotional state on the differentiated self-assessment of functional status test and “quality of life” according to test SF-36. In children of the first group with early surgical correction regarding (under 2 years) significant changes in functionality were noted: higher initial rehabilitation potential and positive changes in central and peripheral hemodynamics, positive changes in the emotional sphere traced by the level of comfort, improved exercise tolerance under the influence of sanatorium rehabilitation. Preliminary observations suggest the possibility of compensation of impaired functions in children of the specified contingent during the sanatorium stage of rehabilitation is to improve their sano-genetic and psycho-physiological potential.

scholarly journals Hey2 restricts cardiac progenitor addition to the developing heart

2017 ◽  
Author(s):  
Natalie Gibb ◽  
Savo Lazic ◽  
Ashish R. Deshwar ◽  
Xuefei Yuan ◽  
Michael D. Wilson ◽  
...  
Keyword(s):  
Heart Development ◽  
Heart Defects ◽  
Myocardial Cell ◽  
Cell Number ◽  
Tube Formation ◽  
Heart Tube ◽  
Cardiac Progenitors ◽  
Developing Heart ◽  
Heart Field ◽  
A Cell

ABSTRACTA key event in vertebrate heart development is the timely addition of second heart field (SHF) progenitor cells to the poles of the heart tube. This accretion process must occur to the proper extent to prevent a spectrum of congenital heart defects (CHDs). However, the factors that regulate this critical process are poorly understood. Here we demonstrate that Hey2, a bHLH transcriptional repressor, restricts SHF progenitor accretion to the zebrafish heart. hey2 expression demarcated a distinct domain within the cardiac progenitor population. In the absence of Hey2 function an increase in myocardial cell number and SHF progenitors was observed. We found that Hey2 limited proliferation of SHF-derived cardiomyocytes in a cell-autonomous manner, prior to heart tube formation, and further restricted the developmental window over which SHF progenitors were deployed to the heart. Taken together, our data suggests a role for Hey2 in controlling the proliferative capacity and cardiac contribution of late-differentiating cardiac progenitors.

scholarly journals Semaphorin3f as an intrinsic regulator of chamber-specific heart development

2021 ◽  
Author(s):  
Rami Halabi ◽  
Paula B. Cechmanek ◽  
Carrie L. Hehr ◽  
Sarah McFarlane
Keyword(s):  
Congenital Heart Defects ◽  
Heart Development ◽  
Congenital Heart ◽  
Molecular Mechanisms ◽  
Heart Defects ◽  
Border Region ◽  
Specific Gene ◽  
Atrioventricular Canal ◽  
Term Survival ◽  
Ventricular Cardiomyocytes

During development a pool of precursors form a heart with atrial and ventricular chambers that exhibit distinct transcriptional and electrophysiological properties. Normal development of these chambers is essential for full term survival of the fetus, and deviations result in congenital heart defects. The large number of genes that may cause congenital heart defects when mutated, and the genetic variability and penetrance of the ensuing phenotypes, reveals a need to understand the molecular mechanisms that allow for the formation of chamber-specific cardiomyocyte differentiation. We find that in the developing zebrafish heart, mRNA for a secreted Semaphorin (Sema), Sema3fb, is expressed by all cardiomyocytes, whereas mRNA for its receptor Plexina3 (Plxna3) is expressed by ventricular cardiomyocytes. In sema3fb CRISPR zebrafish mutants, ventricular chamber development is impaired; the ventricles of mutants are smaller in size than their wild type siblings, apparently because of differences in cell size and not cell numbers, with ventricular cardiomyocytes failing to undergo normal developmental hypertrophy. Analysis of chamber differentiation indicates defects in chamber specific gene expression at the border between the ventricular and atrial chambers, with spillage of ventricular chamber genes into the atrium, and vice versa, and a failure to restrict bmp4a mRNA to the atrioventricular canal. The disrupted atrioventricular border region in mutants is accompanied by hypoplastic heart chambers and impaired cardiac function. These data suggest a model whereby cardiomyocytes secrete a Sema cue that, through spatially restricted expression of the receptor, signals in a ventricular chamber-specific manner to establish a distinct border between atrial and ventricular chambers that is important for functional development of the heart.

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