scholarly journals Sapropterin Treatment Prevents Congenital Heart Defects Induced by Pregestational Diabetes in Mice

2018 ◽  
Author(s):  
Anish Engineer ◽  
Tana Saiyin ◽  
Xiangru Lu ◽  
Andrew S. Kucey ◽  
Brad L. Urquhart ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Congenital Heart Defects ◽  
Congenital Heart ◽  
Fetal Heart ◽  
Heart Defects ◽  
Lineage Tracing ◽  
Endocardial Cushions ◽  
Pregestational Diabetes ◽  
Diabetes In Mice ◽  
Enos Uncoupling

ABSTRACTAimsTetrahydrobiopterin (BH4) is a co-factor of endothelial nitric oxide synthase (eNOS), which is critical to embryonic heart development. We aimed to study the effects of sapropterin (Kuvan®), an orally active synthetic form of BH4 on eNOS uncoupling and congenital heart defects (CHDs) induced by pregestational diabetes in mice.MethodsAdult female mice were induced to pregestational diabetes by streptozotocin and bred with normal males to produce offspring. Pregnant mice were treated with sapropterin or vehicle during gestation. CHDs were identified by histological analysis. Cell proliferation, eNOS dimerization and reactive oxygen species (ROS) production were assessed in the fetal heart.ResultsPregestational diabetes results in a spectrum of CHDs in their offspring. Oral treatment with sapropterin in the diabetic dams significantly decreased the incidence of CHDs from 59% to 27% and major abnormalities, such as atrioventricular septal defect and double outlet right ventricle were absent in the sapropterin treated group. Lineage tracing reveals that pregestational diabetes results in decreased commitment of second heart field progenitors to the outflow tract, endocardial cushions, and ventricular myocardium of the fetal heart. Notably, decreased cell proliferation and cardiac transcription factor expression induced by maternal diabetes were normalized with sapropterin treatment. Furthermore, sapropterin administration in the diabetic dams increased eNOS dimerization and lowered ROS levels in the fetal heart.ConclusionsSapropterin treatment in the diabetic mothers improves eNOS coupling, increases cell proliferation and prevents the development of CHDs in the offspring. Thus, sapropterin may have therapeutic potential in preventing CHDs in pregestational diabetes.

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.

657: Intrapartum fetal heart rate characteristics of fetuses with trisomy 21 and congenital heart defects

2011 ◽  
Vol 204 (1) ◽  
pp. S259-S260
Author(s):  
Priyadarshini Koduri ◽  
Maria Adelaida Giraldo ◽  
Phillip Shlossman ◽  
Anthony Sciscione ◽  
Vincenzo Berghella ◽  
...  
Keyword(s):  
Heart Rate ◽  
Congenital Heart Defects ◽  
Fetal Heart Rate ◽  
Trisomy 21 ◽  
Congenital Heart ◽  
Fetal Heart ◽  
Heart Defects

scholarly journals Maternal Obesity and the Risk of Congenital Heart Defects: the Mediation Effect of Pregestational Diabetes

2021 ◽  
Author(s):  
Xiao-Xia Wu ◽  
Ru-Xiu Ge ◽  
Le Huang ◽  
Fu-Ying Tian ◽  
Yi-Xuan Chen ◽  
...  
Keyword(s):  
Risk Factor ◽  
Congenital Heart Defects ◽  
Congenital Heart ◽  
Maternal Education ◽  
Maternal Obesity ◽  
Heart Defects ◽  
Normal Weight ◽  
Mediation Effect ◽  
Pregestational Diabetes ◽  
Increased Risk

Abstract Background Congenital heart defects (CHDs) are the most common birth defects worldwide. Maternal obesity has been proposed as a risk factor for CHDs, but the results are controversial and inconclusive. Pregestational diabetes (PGDM) is well known as a risk factor for CHDs and is closely related to obesity. However, the effect of PGDM on the association between maternal obesity and CHDs has not been investigated.Objectives We aimed to explore the association between maternal obesity and CHDs and to further evaluate the mediation effect of PGDM on this association.Methods We involved 53708 mother-infant pairs with deliveries between 2017 and 2019 from the Birth Cohort in Shenzhen (BiCoS). Mothers were categorized into four groups: the underweight group (BMI < 18.5), normal weight group (18.5 ≤ BMI < 24), overweight group (24 ≤ BMI < 28) and obesity group (BMI ≥ 28). To evaluate the association between BMI and CHDs, we fit multivariable logistic regression models, adjusting for maternal age, maternal education level, mode of conception, parity, GDM and offspring sex. Mediation analysis was used to confirm the mediation effect of PGDM on the association between maternal obesity and CHDs.Results The proportion of obese individuals in the BiCoS was 2.11%. Overall, 372 (0.69%) infants were diagnosed with CHDs. The prevalence of CHDs in underweight, normal weight, overweight and obese individuals was 0.64%, 0.68%, 0.72% and 1.24%, respectively. Maternal obesity was associated with an increased risk of CHDs (OR=1.97, 95% CI 1.14–3.41). The offspring of women with PGDM were 6.88 times (95% CI 4.11–11.53) more likely to have CHDs than the offspring of mothers without PGDM. The mediation effect of PGDM on the association between maternal obesity and CHDs was significant (OR=1.18, 95% CI 1.06–1.32). The estimated mediation proportion was 24.83%.Conclusion Our findings suggested that maternal obesity was associated with CHDs and that PGDM partially mediated the association between maternal obesity and CHDs.

scholarly journals Maternal biomarkers for fetal heart failure in fetuses with congenital heart defects or arrhythmias

2019 ◽  
Vol 220 (1) ◽  
pp. 104.e1-104.e15 ◽  
Author(s):  
Takekazu Miyoshi ◽  
Hiroshi Hosoda ◽  
Michikazu Nakai ◽  
Kunihiro Nishimura ◽  
Mikiya Miyazato ◽  
...  
Keyword(s):  
Heart Failure ◽  
Congenital Heart Defects ◽  
Congenital Heart ◽  
Fetal Heart ◽  
Heart Defects ◽  
Fetal Heart Failure

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 Sapropterin Treatment Prevents Congenital Heart Defects Induced by Pregestational Diabetes Mellitus in Mice

2018 ◽  
Vol 7 (21) ◽  
Author(s):  
Anish Engineer ◽  
Tana Saiyin ◽  
Xiangru Lu ◽  
Andrew S. Kucey ◽  
Brad L. Urquhart ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Congenital Heart Defects ◽  
Congenital Heart ◽  
Heart Defects ◽  
Pregestational Diabetes

scholarly journals Deep Learning-Based Computer-Aided Fetal Echocardiography: Application to Heart Standard View Segmentation for Congenital Heart Defects Detection

Sensors ◽  
2021 ◽  
Vol 21 (23) ◽  
pp. 8007
Author(s):  
Siti Nurmaini ◽  
Muhammad Naufal Rachmatullah ◽  
Ade Iriani Sapitri ◽  
Annisa Darmawahyuni ◽  
Bambang Tutuko ◽  
...  
Keyword(s):  
Deep Learning ◽  
Congenital Heart Defects ◽  
Congenital Heart ◽  
Fetal Heart ◽  
Fetal Echocardiography ◽  
Heart Defects ◽  
Disease Diagnosis ◽  
Detection Techniques ◽  
Accuracy Of Measurements ◽  
Computer Aided

Accurate segmentation of fetal heart in echocardiography images is essential for detecting the structural abnormalities such as congenital heart defects (CHDs). Due to the wide variations attributed to different factors, such as maternal obesity, abdominal scars, amniotic fluid volume, and great vessel connections, this process is still a challenging problem. CHDs detection with expertise in general are substandard; the accuracy of measurements remains highly dependent on humans’ training, skills, and experience. To make such a process automatic, this study proposes deep learning-based computer-aided fetal heart echocardiography examinations with an instance segmentation approach, which inherently segments the four standard heart views and detects the defect simultaneously. We conducted several experiments with 1149 fetal heart images for predicting 24 objects, including four shapes of fetal heart standard views, 17 objects of heart-chambers in each view, and three cases of congenital heart defect. The result showed that the proposed model performed satisfactory performance for standard views segmentation, with a 79.97% intersection over union and 89.70% Dice coefficient similarity. It also performed well in the CHDs detection, with mean average precision around 98.30% for intra-patient variation and 82.42% for inter-patient variation. We believe that automatic segmentation and detection techniques could make an important contribution toward improving congenital heart disease diagnosis rates.

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