Quantifying Function in the Early Embryonic Heart

2013 ◽  
Vol 135 (4) ◽  
Author(s):  
Brennan M. Johnson ◽  
Deborah M. Garrity ◽  
Lakshmi Prasad Dasi
Keyword(s):  
Cardiac Function ◽  
Heart Development ◽  
Heart Function ◽  
Control Volume ◽  
Heart Defects ◽  
Zebrafish Model ◽  
Cardiac Morphogenesis ◽  
Luminal Diameter ◽  
Early Stages ◽  
Bright Field Microscopy

Congenital heart defects arise during the early stages of development, and studies have linked abnormal blood flow and irregular cardiac function to improper cardiac morphogenesis. The embryonic zebrafish offers superb optical access for live imaging of heart development. Here, we build upon previously used techniques to develop a methodology for quantifying cardiac function in the embryonic zebrafish model. Imaging was performed using bright field microscopy at 1500 frames/s at 0.76 μm/pixel. Heart function was manipulated in a wild-type zebrafish at ∼55 h post fertilization (hpf). Blood velocity and luminal diameter were measured at the atrial inlet and atrioventricular junction (AVJ) by analyzing spatiotemporal plots. Control volume analysis was used to estimate the flow rate waveform, retrograde fractions, stroke volume, and cardiac output. The diameter and flow waveforms at the inlet and AVJ are highly repeatable between heart beats. We have developed a methodology for quantifying overall heart function, which can be applied to early stages of zebrafish development.

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 Genome Wide Meta-Analysis identifies common genetic signatures shared by heart function and Alzheimer’s disease

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
M. E. Sáez ◽  
A. González-Pérez ◽  
B. Hernández-Olasagarre ◽  
A. Beà ◽  
S. Moreno-Grau ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cardiac Function ◽  
Heart Development ◽  
Heart Function ◽  
Meta Analysis ◽  
Genome Wide ◽  
Study Results ◽  
Apoptotic Genes ◽  
The Impact

Abstract Echocardiography has become an indispensable tool for the study of heart performance, improving the monitoring of individuals with cardiac diseases. Diverse genetic factors associated with echocardiographic measures have been previously reported. The impact of several apoptotic genes in heart development identified in experimental models prompted us to assess their potential association with human cardiac function. This study aimed at investigating the possible association of variants of apoptotic genes with echocardiographic traits and to identify new genetic markers associated with cardiac function. Genome wide data from different studies were obtained from public repositories. After quality control and imputation, a meta-analysis of individual association study results was performed. Our results confirmed the role of caspases and other apoptosis related genes with cardiac phenotypes. Moreover, enrichment analysis showed an over-representation of genes, including some apoptotic regulators, associated with Alzheimer’s disease. We further explored this unexpected observation which was confirmed by genetic correlation analyses. Our findings show the association of apoptotic gene variants with echocardiographic indicators of heart function and reveal a novel potential genetic link between echocardiographic measures in healthy populations and cognitive decline later on in life. These findings may have important implications for preventative strategies combating Alzheimer’s disease.

scholarly journals From Stripes to a Beating Heart: Early Cardiac Development in Zebrafish

2021 ◽  
Vol 8 (2) ◽  
pp. 17
Author(s):  
Cassie L. Kemmler ◽  
Fréderike W. Riemslagh ◽  
Hannah R. Moran ◽  
Christian Mosimann
Keyword(s):  
Congenital Heart Defects ◽  
Heart Development ◽  
Congenital Heart ◽  
Cardiac Development ◽  
Heart Defects ◽  
Lineage Tracing ◽  
Genetic Lineage ◽  
Zebrafish Model ◽  
Lateral Plate ◽  
Cardiac Progenitors

The heart is the first functional organ to form during vertebrate development. Congenital heart defects are the most common type of human birth defect, many originating as anomalies in early heart development. The zebrafish model provides an accessible vertebrate system to study early heart morphogenesis and to gain new insights into the mechanisms of congenital disease. Although composed of only two chambers compared with the four-chambered mammalian heart, the zebrafish heart integrates the core processes and cellular lineages central to cardiac development across vertebrates. The rapid, translucent development of zebrafish is amenable to in vivo imaging and genetic lineage tracing techniques, providing versatile tools to study heart field migration and myocardial progenitor addition and differentiation. Combining transgenic reporters with rapid genome engineering via CRISPR-Cas9 allows for functional testing of candidate genes associated with congenital heart defects and the discovery of molecular causes leading to observed phenotypes. Here, we summarize key insights gained through zebrafish studies into the early patterning of uncommitted lateral plate mesoderm into cardiac progenitors and their regulation. We review the central genetic mechanisms, available tools, and approaches for modeling congenital heart anomalies in the zebrafish as a representative vertebrate model.

scholarly journals Applicability and technical aspects of two-dimensional ultrasonography for assessment of fetal heart function

2017 ◽  
Vol 19 (1) ◽  
pp. 94 ◽  
Author(s):  
Nathalie Jeanne Bravo-valenzuela ◽  
Alberto Borges Peixoto ◽  
Luciano Marcondes Nardozza ◽  
Alex Sandro Souza ◽  
Edward Araujo Júnior
Keyword(s):  
Cardiac Function ◽  
Fetal Heart ◽  
Heart Function ◽  
Fetal Echocardiography ◽  
Myocardial Dysfunction ◽  
Heart Defects ◽  
Systemic Disease ◽  
Volume Overload ◽  
Fetal Cardiac Function ◽  
Echocardiographic Parameters

In recent years, fetal echocardiography has been used for the screening and diagnosis of anatomical heart defects and for the detailed study of fetal cardiac function. This method is characterized by its easy implementation and good reproducibility, allowing the diagnosis of myocardial dysfunction even in its subclinical phase. The functional assessment of the fetal heart should be routinely performed in fetuses with congenital heart disease and those without anatomical malformation. Several extra-cardiac conditions may alter fetal cardiac function, by increased placental resistance, volume overload or hyperdynamic circulation, compression, or maternal systemic disease with involvement of the fetal myocardium. This review addresses the main ultrasound techniques and various Doppler echocardiographic parameters available for the analysis of fetal heart function, and correlates them with clinical applicability. Various parameters available for the assessment of fetal myocardium, including those that evaluate atrial dynamics, can be used in this analysis and should be selected considering specific conditions.

scholarly journals Palmitoyl acyltransferase Aph2 in cardiac function and the development of cardiomyopathy

2015 ◽  
Vol 112 (51) ◽  
pp. 15666-15671 ◽  
Author(s):  
Tielin Zhou ◽  
Jing Li ◽  
Peiquan Zhao ◽  
Huijuan Liu ◽  
Deyong Jia ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Protein Phosphatase ◽  
Heart Development ◽  
Cell Function ◽  
Physiological Function ◽  
Heart Defects ◽  
Protein Phosphatase 1 ◽  
Protein Palmitoylation ◽  
Palmitoyl Acyltransferase

Protein palmitoylation regulates many aspects of cell function and is carried out by acyl transferases that contain zf-DHHC motifs. The in vivo physiological function of protein palmitoylation is largely unknown. Here we generated mice deficient in the acyl transferase Aph2 (Ablphilin 2 or zf-DHHC16) and demonstrated an essential role for Aph2 in embryonic/postnatal survival, eye development, and heart development. Aph2−/− embryos and pups showed cardiomyopathy and cardiac defects including bradycardia. We identified phospholamban, a protein often associated with human cardiomyopathy, as an interacting partner and a substrate of Aph2. Aph2-mediated palmitoylation of phospholamban on cysteine 36 differentially alters its interaction with PKA and protein phosphatase 1 α, augmenting serine 16 phosphorylation, and regulates phospholamban pentamer formation. Aph2 deficiency results in phospholamban hypophosphorylation, a hyperinhibitory form. Ablation of phospholamban in Aph2−/− mice histologically and functionally alleviated the heart defects. These findings establish Aph2 as a critical in vivo regulator of cardiac function and reveal roles for protein palmitoylation in the development of other organs including eyes.

scholarly journals Genome Wide Meta-Analysis identifies new loci associated with cardiac phenotypes and uncovers a common genetic signature shared by heart function and Alzheimer’s disease

2018 ◽  
Author(s):  
MªEugenia Sáez ◽  
Antonio González-Pérez ◽  
Begoña Hernández-Olasagarre ◽  
Aida Beà ◽  
Sonia Moreno-Grau ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cardiac Function ◽  
Heart Development ◽  
Heart Function ◽  
Experimental Models ◽  
Association Analyses ◽  
Genome Wide ◽  
Apoptotic Genes ◽  
The Impact

ABSTRACTAimsEchocardiography has become an indispensable tool for the study of heart performance, improving the monitoring of individuals with cardiac diseases. Diverse genetic factors associated with echocardiographic measures of heart structure and functions have been previously reported. The impact of several apoptotic genes in heart development identified in experimental models prompted us to assess their potential association with indicators of human cardiac function. This study started with the aim to investigate the possible association of variants of apoptotic genes with echocardiographic traits and to identify new genetic markers associated with cardiac function.Methods and resultsGenome wide data from different studies were obtained from public repositories. After quality control and imputation, association analyses confirm the role of caspases and other apoptosis related genes with cardiac phenotypes. Moreover, enrichment analysis showed an over-representation of genes, including some apoptotic regulators, associated with Alzheimer’s disease (AD). We further explored this unexpected observation which was confirmed by genetic correlation analyses.ConclusionsOur findings show the association of apoptotic gene variants with echocardiographic indicators of heart function and reveal a novel potential genetic link between echocardiographic measures in healthy populations and cognitive decline later on in life. These findings may have important implications for preventative strategies combating Alzheimer’s disease.

Atrial natriuretic factor in the developing heart: a signpost for cardiac morphogenesis

2011 ◽  
Vol 89 (8) ◽  
pp. 533-537 ◽  
Author(s):  
Benoit G. Bruneau
Keyword(s):  
Heart Development ◽  
Atrial Natriuretic Factor ◽  
Heart Defects ◽  
Deep Understanding ◽  
Cardiac Morphogenesis ◽  
Molecular Defects ◽  
Natriuretic Factor ◽  
Developing Heart ◽  
Dynamic Expression ◽  
Atrial Natriuretic

The developing heart forms during the early stages of embryogenesis, and misregulated heart development results in congenital heart defects (CHDs). To understand the molecular basis of CHDs, a deep understanding of the morphological and genetic basis of heart development is necessary. Atrial Natriuretic Factor (ANF) is an important and extremely sensitive marker for specific regions of the developing heart, as well as for disturbances in the patterning of the heart. This review summarizes the dynamic expression of ANF in the developing heart and its usefulness in understanding the early molecular defects underlying CHDs.

scholarly journals First report of polymorphisms in MTRR, GATA4, VEGF, and ISL1 genes in Pakistani children with isolated ventricular septal defects (VSD)

2021 ◽  
Vol 47 (1) ◽  
Author(s):  
Sumbal Sarwar ◽  
Farah Ehsan ◽  
Shabana ◽  
Amna Tahir ◽  
Mahrukh Jamil ◽  
...  
Keyword(s):  
Heart Development ◽  
Heart Defects ◽  
Demographic Data ◽  
Gene Variant ◽  
Nucleotide Polymorphisms ◽  
Ventricular Septal Defects ◽  
First Report ◽  
Number Of Children ◽  
Septal Defects ◽  
Genotype Frequencies

Abstract Background Ventricular septal defects (VSDs) are malformations in the septum separating the heart’s ventricles. VSDs may present as a single anomaly (isolated/nonsyndromic VSD) or as part of a group of phenotypes (syndromic VSD). The exact location of the defect is crucial in linking the defect to the underlying genetic cause. The number of children visiting cardiac surgery units is constantly increasing. However, there are no representative data available on the genetics of VSDs in Pakistani children. Methods Two hundred forty-two subjects (121 VSD children and 121 healthy controls) were recruited from pediatric cardiac units of Lahore. The clinical and demographic data of the subjects were collected. A total of four SNPs, one each from MTRR, GATA4, VEGF, and ISL1 genes were genotyped by PCR-RFLP. Results The results showed that the minor allele (T) frequency (MAFs) for the MTRR gene variant rs1532268 (c.524C > T) was 0.20 and 0.41 in the controls and the cases, respectively, with the genotype frequencies 3, 35, 62% in the controls and 12, 59 and 29% in the cases for TT, CT, CC genotypes, respectively (allelic OR: 5.73, CI: 3.82–8.61, p-value: 5.11 × 10− 7). For the GATA4 variant rs104894073 (c.886G > A), the MAF for the controls and the cases was 0.16 and 0.37, respectively, the frequencies of AA, GA and GG genotypes were 2, 28, and 70% in the controls and 5, 64 and 31% of the cases (allelic OR: 3.08, CI: 2.00–4.74, p-value: 8.36 × 10− 8). The rs699947 (c.-2578C > A) of VEGF gene showed MAF 0.36 and 0.53 for the controls and cases, respectively, with the genotype frequencies 13, 42, and 45% in the controls and 22, 15, and 63% in the cases for the AA, CA, CC (allelic OR: 2.03, CI: 1.41–2.92, p-value: 0.0001). The ISL1 gene variant rs6867206 (g.51356860 T > C), the MAFs were 0.26 and 0.31 in the controls and cases, respectively. The genotype frequencies were 48, 52, 0% in the controls and 39, 61, 0% in the cases for TT, TC, CC genotypes (allelic OR: 0.27, CI: 0.85–1.89, p-value: 0.227). The MTRR, GATA4 and VEGF variants showed association while ISL1 variant did not appear to be associated with the VSD in the recruited cohort. Conclusion This first report in Pakistani children demonstrates that single nucleotide polymorphisms in genes encoding transcription factors, signaling molecules and structural heart genes involved in fetal heart development are associated with developmental heart defects., however further work is needed to validate the results of the current investigation.

CMR fast-SENC segmental intramyocardial LV strain monitors decline in heart function before ejection fraction in patient with mitral valve disease

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Montenbruck ◽  
S Kelle ◽  
S Esch ◽  
A.K Schwarz ◽  
S Giusca ◽  
...  
Keyword(s):  
Mitral Valve ◽  
Ejection Fraction ◽  
Cardiac Function ◽  
Mitral Valve Disease ◽  
Heart Function ◽  
Global Longitudinal Strain ◽  
Image Plane ◽  
Valve Disease ◽  
Peak Strain ◽  
Regional Dysfunction

Abstract Background Ejection fraction is the standard metric to analyze cardiac function in the left (LV) or right (RV) ventricles. However, these global metrics are not able to characterize patients in which the heart compensates for regional dysfunction. More sensitive metrics are needed to detect subclinical regional dysfunction before cardiac remodeling results in changes in ejection fraction (EF) and global longitudinal strain (GLS). Fast-SENC intramyocardial strain (fSENC) is a unique cardiac magnetic resonance imaging (CMR) modality that measures intramyocardial contraction in 1 heartbeat per image plane. This prospective registry compares segmental fSENC to standard CMR calculations (e.g. LVEF, volumes, mass, etc.) in patients with mitral valve disease. Methods A single center, prospective registry of CMR scans acquired with a 1.5T scanner were evaluated for standard CMR calculations as well as fSENC scans. Intramyocardial LV & RV strain was quantified with MyoStrain software. Three short axis scans (basal, midventricular, & apical) were used to calculate peak strain in 16 LV & 6 RV longitudinal segments while three long axis scans (2-, 3-, & 4-chamber) were used to calculate 21 LV & 5 RV circumferential segments. Results A total of 493 scans in 424 patients with moderate or severe mitral regurgitation were included in the study. Patients had an average (± stdev) age of 60 (15) yrs and BMI of 27 (4) kg/m2; 63% had arterial hypertension, 19% diabetes mellitus, 10% atrial fibrillation, 15% pulmonary disease, and 32% coronary artery disease. Figure 1 shows the non-linear relationship between segmental fSENC strain (% of normal LV segments ≤−17%) versus LVEF (R=0.81). Conclusion Segmental fSENC detects subclinical LV dysfunction before changes in LVEF. Evaluating segmental longitudinal and circumferential fSENC peak strain provides an alternative metric that shows consistent changes in cardiac function in patients with mitral valve disease irrespective of global calculations that are dependent on loading conditions. Funding Acknowledgement Type of funding source: None

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.

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