ArticleVascular pharmacology2015
IGF-1 signaling in neonatal hypoxia-induced pulmonary hypertension: Role of epigenetic regulation.
Article in Vascular pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
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Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 citations in OpenAlex.
- Effects of early- and mid-life stress on DNA methylation of genes associated with subclinical cardiovascular disease and cognitive impairment: a systematic review.BMC medical genetics · 2019Pooled it
- The histone deacetylase family in health and disease.Signal transduction and targeted therapy · 2026Review
- Role of Histone Deacetylase and Inhibitors in Cardiovascular Diseases.Cell proliferation · 2025Review
- Echocardiographic Assessment of Pulmonary Hemodynamics and Right Ventricular Performance in Neonatal Murine Hypoxia.Journal of cardiovascular development and disease · 2025Article
- Decoding the enigmatic estrogen paradox in pulmonary hypertension: delving into estrogen metabolites and metabolic enzymes.Cellular & molecular biology letters · 2024Review
- Histone deacetylases: Regulation of vascular homeostasis via endothelial cells and vascular smooth muscle cells and the role in vascular pathogenesis.Genes & diseases · 2024Review
- Identification and experimental verification of senescence-related gene signatures and molecular subtypes in idiopathic pulmonary arterial hypertension.Scientific reports · 2024Article
- Identifying Key Biomarkers in Pediatric Pulmonary Hypertension: An Investigative Approach.Children (Basel, Switzerland) · 2024Article
- Zinc-Dependent Histone Deacetylases in Lung Endothelial Pathobiology.Biomolecules · 2024Review
- Developmental reprogramming of myometrial stem cells by endocrine disruptor linking to risk of uterine fibroids.Cellular and molecular life sciences : CMLS · 2023Article
- Current Therapy and Liver Transplantation for Portopulmonary Hypertension in Japan.Journal of clinical medicine · 2023Review
- Identification of the shared gene signatures between pulmonary fibrosis and pulmonary hypertension using bioinformatics analysis.Frontiers in immunology · 2023Article
- Epigenetic Mechanisms as Emerging Therapeutic Targets and Microfluidic Chips Application in Pulmonary Arterial Hypertension.Biomedicines · 2022Review
- Mechanism of histone deacetylases in cardiac hypertrophy and its therapeutic inhibitors.Frontiers in cardiovascular medicine · 2022Review
- Identification of autophagy-related biomarkers in patients with pulmonary arterial hypertension based on bioinformatics analysis.Open medicine (Warsaw, Poland) · 2022Article
- Hepatopulmonary syndrome as the first and only manifestation of cirrhosis in a patient with hypopituitarism.BMJ case reports · 2021Article
- Exposomes to Exosomes: Exosomes as Tools to Study Epigenetic Adaptive Mechanisms in High-Altitude Humans.International journal of environmental research and public health · 2021Review
- Article
- Pregnancy-associated plasma protein A - a new indicator of pulmonary vascular remodeling in chronic thromboembolic pulmonary hypertension?Respiratory research · 2020Article
- Lysine acetyltransferases and lysine deacetylases as targets for cardiovascular disease.Nature reviews. Cardiology · 2020Review
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Pulmonary hypertension is a fatal disease characterized by a progressive increase in pulmonary artery pressure accompanied by pulmonary vascular remodeling and increased vasomotor tone. Although some biological pathways have been identified in neonatal hypoxia-induced pulmonary hypertension (PH), little is known regarding the role of growth factors in the pathogenesis of PH in neonates. In this study, using a model of hypoxia-induced PH in neonatal mice, we demonstrate that the growth factor insulin-like growth factor-1 (IGF-1), a potent activator of the AKT signaling pathway, is involved in neonatal PH. After exposure to hypoxia, IGF-1 signaling is activated in pulmonary endothelial and smooth muscle cells in vitro, and the IGF-1 downstream signal pAKT(S473) is upregulated in lungs of neonatal mice. We found that IGF-1 regulates ET-1 expression in pulmonary endothelial cells and that IGF-1 expression is regulated by histone deacetylases (HDACs). In addition, there is a differential cytosine methylation site in the IGF-1 promoter region in response to neonatal hypoxia. Moreover, inhibition of HDACs with apicidin decreases neonatal hypoxia-induced global DNA methylation levels in lungs and specific cytosine methylation levels around the pulmonary IGF-1 promoter region. Finally, HDAC inhibition with apicidin reduces chronic hypoxia-induced activation of IGF-1/pAKT signaling in lungs and attenuates right ventricular hypertrophy and pulmonary vascular remodeling. Taken together, we conclude that IGF-1, which is epigenetically regulated, is involved in the pathogenesis of pulmonary hypertension in neonatal mice. This study implicates a novel HDAC/IGF-1 epigenetic pathway in the regulation of hypoxia-induced PH and warrants further study of the role of IGF-1 in neonatal pulmonary hypertensive disease.
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