ArticleFrontiers in pharmacology2015
Hypoxia inducible factor signaling and experimental persistent pulmonary hypertension of the newborn.
Article in Frontiers in pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 27 citations in OpenAlex.
- Stub1 Acetylation by CBP/p300 Attenuates Chronic Hypoxic-Driven Pulmonary Hypertension by Suppressing HIF-2α.American journal of respiratory cell and molecular biology · 2025Article
- Glycolysis modulation: New therapeutic strategies to improve pulmonary hypertension (Review).International journal of molecular medicine · 2024Review
- Mechanism of Hypoxia-Mediated Smooth Muscle Cell Proliferation Leading to Vascular Remodeling.BioMed research international · 2022Review
- Management Practices During Perinatal Respiratory Transition of Very Premature Infants.Frontiers in pediatrics · 2022Review
- Design of a synthesis-friendly hypoxia-responsive promoter for cell-based therapeutics.Engineering in life sciences · 2021Article
- Pediatric Pulmonary Hypertension: Definitions, Mechanisms, Diagnosis, and Treatment.Comprehensive Physiology · 2021Article
- Risk Factors and Outcomes of Acute Kidney Injury in Neonates with Persistent Pulmonary Hypertension of the Newborn.Medeniyet medical journal · 2021Article
- Hypoxia-inducible factor signaling in pulmonary hypertension.The Journal of clinical investigation · 2020Review
- Thiol-Redox Regulation in Lung Development and Vascular Remodeling.Antioxidants & redox signaling · 2019Review
- Revisiting the role of hypoxia-inducible factors in pulmonary hypertension.Current opinion in physiology · 2019Article
- Altered hypoxia-inducible factor-1α (HIF-1α) signaling contributes to impaired angiogenesis in fetal lambs with persistent pulmonary hypertension of the newborn (PPHN).Physiological reports · 2019Article
- [Effect of calcium-sensitive receptors on endothelial nitric oxide synthase and nitric oxide in neonatal mice with persistent pulmonary hypertension].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2019Article
- Gestational Hypoxia and Developmental Plasticity.Physiological reviews · 2018Review
- Chronic lifestyle diseases display seasonal sensitive comorbid trend in human population evidence from Google Trends.PloS one · 2018Article
- Melatonin Decreases Pulmonary Vascular Remodeling and Oxygen Sensitivity in Pulmonary Hypertensive Newborn Lambs.Frontiers in physiology · 2018Article
- Opsin 3 and 4 mediate light-induced pulmonary vasorelaxation that is potentiated by G protein-coupled receptor kinase 2 inhibition.American journal of physiology. Lung cellular and molecular physiology · 2018Article
- Effects of FHL1 and P21 on hypoxia-induced pulmonary vascular remodeling in neonatal rats.Experimental and therapeutic medicine · 2017Article
- Endothelial Cell Reactive Oxygen Species and CaAdvances in experimental medicine and biology · 2017Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundMitochondrial reactive oxygen species (ROS) levels and nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) activity are increased in a lamb model of persistent pulmonary hypertension of the newborn (PPHN). These events can trigger hypoxia inducible factor (HIF) signaling in response to hypoxia, which has been shown to contribute to pulmonary vascular remodeling in rodent models of pulmonary hypertension. However, the role of HIF signaling in chronic intrauterine pulmonary hypertension is not well understood.
aimTo determine if HIF signaling is increased in the lamb model of PPHN, and to identify the underlying mechanisms.
resultsPPHN was induced in lambs by antenatal ligation of the ductus arteriosus at 128 days gestation. After 9 days, lungs and pulmonary artery smooth muscle cells (PASMC) were isolated from control and PPHN lambs. HIF-1α expression was increased in PPHN lungs and HIF activity was increased in PPHN PASMC relative to controls. Hypoxia increased HIF activity to a greater degree in PPHN vs. control PASMC. Control PASMC were exposed to cyclic stretch at 1 Hz and 15% elongation for 24 h, as an in vitro model of vascular stress. Stretch increased HIF activity, which was attenuated by inhibition of mitochondrial complex III and NFκB.
conclusionIncreased HIF signaling in PPHN is triggered by stretch, via mechanisms involving mitochondrial ROS and NFκB. Hypoxia substantially amplifies HIF activity in PPHN vascular cells. Targeting these signaling molecules may attenuate and reverse pulmonary vascular remodeling associated with PPHN.
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