ArticleInternational journal of medical sciences2014
Endothelin-1 promotes cardiomyocyte terminal differentiation in the developing heart via heightened DNA methylation.
Article in International journal of medical sciences, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 34 citations in OpenAlex.
- Understanding physiological adaptations of pregnancy to the chronic hypoxia of high altitude to inform obstetrical and neonatal care.Physiological reviews · 2026Review
- Whole transcriptome profiling of prospective endomyocardial biopsies reveals prognostic and diagnostic signatures of cardiac allograft rejection.The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation · 2022Observational
- Sex differences and the effects of intrauterine hypoxia on growth and in vivo heart function of fetal guinea pigs.American journal of physiology. Regulatory, integrative and comparative physiology · 2020Article
- Cardiomyogenesis Modeling Using Pluripotent Stem Cells: The Role of Microenvironmental Signaling.Frontiers in cell and developmental biology · 2019Review
- Gestational Hypoxia and Developmental Plasticity.Physiological reviews · 2018Review
- SIRT1 increases cardiomyocyte binucleation in the heart development.Oncotarget · 2018Article
- Near to One's Heart: The Intimate Relationship Between the Placenta and Fetal Heart.Frontiers in physiology · 2018Review
- Role of DNA methylation in perinatal nicotine-induced development of heart ischemia-sensitive phenotype in rat offspring.Oncotarget · 2017Article
- Effects of β-adrenergic receptor drugs on embryonic ventricular cell proliferation and differentiation and their impact on donor cell transplantation.American journal of physiology. Heart and circulatory physiology · 2017Article
- Proteomic Analysis of Endothelin-1 Targets in the Regulation of Cardiomyocyte Proliferation.Current topics in medicinal chemistry · 2017Article
- Maturation of pluripotent stem cell derived cardiomyocytes: The new challenge.Global cardiology science & practice · 2016Review
- Antenatal hypoxia induces epigenetic repression of glucocorticoid receptor and promotes ischemic-sensitive phenotype in the developing heart.Journal of molecular and cellular cardiology · 2016Article
- Article
- Epigenetic mechanisms in heart development and disease.Drug discovery today · 2015Review
- Article
- How the proteome packages the genome for cardiovascular development.Proteomics · 2014Review
- Small engine, big power: microRNAs as regulators of cardiac diseases and regeneration.International journal of molecular sciences · 2014Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
aimsHypoxia is a major stress on fetal development and leads to induction of endothelin-1 (ET-1) expression. We tested the hypothesis that ET-1 stimulates the terminal differentiation of cardiomyocytes from mononucleate to binucleate in the developing heart. METHODS AND
resultsHypoxia (10.5% O2) treatment of pregnant rats from day 15 to day 21 resulted in a significant increase in prepro-ET-1 mRNA expression in fetal hearts. ET-1 ex vivo treatment of fetal rat cardiomyocytes increased percent binucleate cells and decreased Ki-67 expression, a marker for proliferation, under both control and hypoxic conditions. Hypoxia alone decreased Ki-67 expression and in conjunction with ET-1 treatment decreased cardiomyocyte size. PD145065, a non-selective ET-receptor antagonist, blocked the changes in binucleation and proliferation caused by ET-1. DNA methylation in fetal cardiomyocytes was significantly increased with ET-1 treatment, which was blocked by 5-aza-2'-deoxycytidine, a DNA methylation inhibitor. In addition, 5-aza-2'-deoxycytidine treatment abrogated the increase in binucleation and decrease in proliferation induced by ET-1.
conclusionsHypoxic stress and synthesis of ET-1 increases DNA methylation and promotes terminal differentiation of cardiomyocytes in the developing heart. This premature exit of the cell cycle may lead to a reduced cardiomyocyte endowment in the heart and have a negative impact on cardiac function.
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Registered trials
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