ArticleAmerican journal of physiology. Lung cellular and molecular physiology2016
Decreased endothelial nitric oxide synthase expression and function contribute to impaired mitochondrial biogenesis and oxidative stress in fetal lambs with persistent pulmonary hypertension.
Article in American journal of physiology. Lung cellular and molecular physiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed.
- Early use of combined exogenous surfactant and inhaled nitric oxide reduces treatment failure in persistent pulmonary hypertension of the newborn: a randomized controlled trial.Journal of perinatology : official journal of the California Perinatal Association · 2021Trial
- Advances in the pathogenesis and clinical management of pulmonary hypertension.Medical review (2021) · 2026Review
- ALDOB K87 lactylation drives mitochondrial fission and metabolic reprogramming in pulmonary hypertension.Communications biology · 2026Article
- Early Oxygenation and Mortality in Infants Treated with Inhaled Nitric Oxide (iNO) for Persistent Pulmonary Hypertension of the Newborn (PPHN).Journal of pediatrics. Clinical practice · 2025Article
- Abnormal Fetal/Neonatal Lung Development Manifested as Some Functional Heart Abnormalities During the Third Trimester of Fetal Life.Biomedicines · 2025Article
- ExploringDiagnostics (Basel, Switzerland) · 2025Article
- Signaling pathways and targeted therapy for pulmonary hypertension.Signal transduction and targeted therapy · 2025Review
- Alterations in Mitochondrial Function in Pulmonary Vascular Diseases.Antioxidants & redox signaling · 2025Article
- Aberrant PGC-1α signaling in a lamb model of persistent pulmonary hypertension of the newborn.Pediatric research · 2024Article
- Pde3a and Pde3b regulation of murine pulmonary artery smooth muscle cell growth and metabolism.Physiological reports · 2024Article
- Meconium Aspiration Syndrome, Hypoxic-Ischemic Encephalopathy and Therapeutic Hypothermia-A Recipe for Severe Pulmonary Hypertension?Children (Basel, Switzerland) · 2024Review
- Estrogen-mediated modulation of sterile inflammatory markers and baroreflex sensitivity in ovariectomized female Wistar rats.Archives of endocrinology and metabolism · 2024Article
- Signal Transduction during Metabolic and Inflammatory Reprogramming in Pulmonary Vascular Remodeling.International journal of molecular sciences · 2022Review
- Metabolism, Mitochondrial Dysfunction, and Redox Homeostasis in Pulmonary Hypertension.Antioxidants (Basel, Switzerland) · 2022Review
- Mitochondrial Metabolism, Redox, and Calcium Homeostasis in Pulmonary Arterial Hypertension.Biomedicines · 2022Review
- Pulmonary Resilience: Moderating the Association between Oxygen Exposure and Pulmonary Outcomes in Extremely Preterm Newborns.Neonatology · 2022Review
- Mitochondrial dysfunction in pulmonary arterial hypertension.Frontiers in physiology · 2022Review
- Decreased Cyclic Guanosine Monophosphate-Protein Kinase G Signaling Impairs Angiogenesis in a Lamb Model of Persistent Pulmonary Hypertension of the Newborn.American journal of respiratory cell and molecular biology · 2021Article
- Oxygen Toxicity to the Immature Lung-Part I: Pathomechanistic Understanding and Preclinical Perspectives.International journal of molecular sciences · 2021Review
- Oxygen sensing, mitochondrial biology and experimental therapeutics for pulmonary hypertension and cancer.Free radical biology & medicine · 2021Article
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Authors and funding
7 authors.
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Abstract
Impaired vasodilation in persistent pulmonary hypertension of the newborn (PPHN) is characterized by mitochondrial dysfunction. We investigated the hypothesis that a decreased endothelial nitric oxide synthase level leads to impaired mitochondrial biogenesis and function in a lamb model of PPHN induced by prenatal ductus arteriosus constriction. We ventilated PPHN lambs with 100% O2 alone or with inhaled nitric oxide (iNO). We treated pulmonary artery endothelial cells (PAECs) from normal and PPHN lambs with detaNONOate, an NO donor. We observed decreased mitochondrial (mt) DNA copy number, electron transport chain (ETC) complex subunit levels, and ATP levels in PAECs and lung tissue of PPHN fetal lambs at baseline compared with gestation matched controls. Phosphorylation of AMP-activated kinase (AMPK) and levels of peroxisome proliferator-activated receptor-γ coactivator 1-α (PGC-1α) and sirtuin-1, which facilitate mitochondrial biogenesis, were decreased in PPHN. Ventilation with 100% O2 was associated with larger decreases in ETC subunits in the lungs of PPHN lambs compared with unventilated PPHN lambs. iNO administration, which facilitated weaning of FiO2 , partly restored mtDNA copy number, ETC subunit levels, and ATP levels. DetaNONOate increased eNOS phosphorylation and its interaction with heat shock protein 90 (HSP90); increased levels of superoxide dismutase 2 (SOD2) mRNA, protein, and activity; and decreased the mitochondrial superoxide levels in PPHN-PAECs. Knockdown of eNOS decreased ETC protein levels in control PAECs. We conclude that ventilation with 100% O2 amplifies oxidative stress and mitochondrial dysfunction in PPHN, which are partly improved by iNO and weaning of oxygen.
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