ArticleJournal of the American Heart Association2018
Sapropterin Treatment Prevents Congenital Heart Defects Induced by Pregestational Diabetes Mellitus in Mice.
Article in Journal of the American Heart Association, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- Maternal obesity and metabolic disorders associate with congenital heart defects in the offspring: A systematic review.PloS one · 2021Pooled it
- Long Non-Coding Ribonucleic Acid Taurine Up-Regulated Gene 1 Accelerates Ventricular Septal Defect Formation in Children.Brazilian journal of cardiovascular surgery · 2026Article
- Haploinsufficiency of Endothelial Nitric Oxide Synthase Mitigates Beneficial Effects of Maternal Exercise on Fetal Heart Development During Pregestational Diabetes.Journal of the American Heart Association · 2026Article
- Guidelines for in vivo models of developmental programming of cardiovascular disease risk.American journal of physiology. Heart and circulatory physiology · 2024Review
- ER stress and lipid imbalance drive diabetic embryonic cardiomyopathy in an organoid model of human heart development.Stem cell reports · 2024Article
- Maternal Pre-Existing Diabetes: A Non-Inherited Risk Factor for Congenital Cardiopathies.International journal of molecular sciences · 2023Review
- Research Progress of Maternal Metabolism on Cardiac Development and Function in Offspring.Nutrients · 2023Review
- ER stress and lipid imbalance drive embryonic cardiomyopathy in a human heart organoid model of pregestational diabetes.bioRxiv : the preprint server for biology · 2023Article
- Single-cell transcriptomic profiling unveils dysregulation of cardiac progenitor cells and cardiomyocytes in a mouse model of maternal hyperglycemia.Communications biology · 2022Article
- Maternal nicotine exposure induces congenital heart defects in the offspring of mice.Journal of cellular and molecular medicine · 2022Article
- Modeling the Effects of Maternal Diabetes on the Developing Human Heart Using Pluripotent Stem Cell-Derived Heart Organoids.Current protocols · 2022Article
- Genome-Wide De Novo Variants in Congenital Heart Disease Are Not Associated With Maternal Diabetes or Obesity.Circulation. Genomic and precision medicine · 2022Observational
- Impact of maternal hyperglycemia on cardiac development: Insights from animal models.Genesis (New York, N.Y. : 2000) · 2021Review
- The role of glucose in physiological and pathological heart formation.Developmental biology · 2021Review
- Myocardium-Specific Deletion of Rac1 Causes Ventricular Noncompaction and Outflow Tract Defects.Journal of cardiovascular development and disease · 2021Article
- Incidence and mortality trend of congenital heart disease at the global, regional, and national level, 1990-2017.Medicine · 2020Observational
- Maternal Obesity and Diabetes Mellitus as Risk Factors for Congenital Heart Disease in the Offspring.Journal of the American Heart Association · 2020Review
- Say NO to ROS: Their Roles in Embryonic Heart Development and Pathogenesis of Congenital Heart Defects in Maternal Diabetes.Antioxidants (Basel, Switzerland) · 2019Review
- Maternal voluntary exercise mitigates oxidative stress and incidence of congenital heart defects in pre-gestational diabetes.Journal of cellular and molecular medicine · 2019Article
- Sapropterin Treatment Prevents Congenital Heart Defects Induced by Pregestational Diabetes Mellitus in Mice.Journal of the American Heart Association · 2018Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background Tetrahydrobiopterin is a cofactor of endothelial NO synthase ( eNOS ), which is critical to embryonic heart development. We aimed to study the effects of sapropterin (Kuvan), an orally active synthetic form of tetrahydrobiopterin on eNOS uncoupling and congenital heart defects ( CHD s) induced by pregestational diabetes mellitus in mice. Methods and Results Adult female mice were induced to pregestational diabetes mellitus by streptozotocin and bred with normal male mice to produce offspring. Pregnant mice were treated with sapropterin or vehicle during gestation. CHD s were identified by histological analysis. Cell proliferation, eNOS dimerization, and reactive oxygen species production were assessed in the fetal heart. Pregestational diabetes mellitus results in a spectrum of CHD s in their offspring. Oral treatment with sapropterin in the diabetic dams significantly decreased the incidence of CHD s 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 mellitus 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 mellitus were normalized with sapropterin treatment. Furthermore, sapropterin administration in the diabetic dams increased eNOS dimerization and lowered reactive oxygen species levels in the fetal heart. Conclusions Sapropterin treatment in the diabetic mothers improves eNOS coupling, increases cell proliferation, and prevents the development of CHD s in the offspring. Thus, sapropterin may have therapeutic potential in preventing CHD s in pregestational diabetes mellitus.
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