ArticlePediatric research2013
Endothelin-1 impairs angiogenesis in vitro through Rho-kinase activation after chronic intrauterine pulmonary hypertension in fetal sheep.
Article in Pediatric research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 45 citations in OpenAlex.
- Activin A-Endothelin-1 Axis Governs Pulmonary Vascular Remodeling: Mechanistic Basis for Emerging Therapies in PAH.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- Myosin light chain phosphatase is a downstream target of Rho-kinase in endothelin-1-induced transactivation of the TGF-β receptor.Cell biochemistry and biophysics · 2024Article
- Pulmonary hypertension in the newborn- etiology and pathogenesis.Seminars in fetal & neonatal medicine · 2022Review
- Endothelial dysfunction in preterm infants: The hidden legacy of uteroplacental pathologies.Frontiers in pediatrics · 2022Review
- Pediatric Pulmonary Hypertension: Definitions, Mechanisms, Diagnosis, and Treatment.Comprehensive Physiology · 2021Article
- Monitoring Endothelin-A Receptor Expression during the Progression of Atherosclerosis.Biomedicines · 2020Article
- Glomerular Endothelial Cells as Instigators of Glomerular Sclerotic Diseases.Frontiers in pharmacology · 2020Review
- Persistent Pulmonary Hypertension of the Newborn: Pathophysiological Mechanisms and Novel Therapeutic Approaches.Frontiers in pediatrics · 2020Review
- Gestational Hypoxia and Developmental Plasticity.Physiological reviews · 2018Review
- Endothelin-1-Rho kinase interactions impair lung structure and cause pulmonary hypertension after bleomycin exposure in neonatal rat pups.American journal of physiology. Lung cellular and molecular physiology · 2016Article
- Chronic anemic hypoxemia increases plasma glucagon and hepatic PCK1 mRNA in late-gestation fetal sheep.American journal of physiology. Regulatory, integrative and comparative physiology · 2016Article
- Challenges, priorities and novel therapies for hypoxemic respiratory failure and pulmonary hypertension in the neonate.Journal of perinatology : official journal of the California Perinatal Association · 2016Review
- Pharmacologic strategies in neonatal pulmonary hypertension other than nitric oxide.Seminars in perinatology · 2016Review
- Impaired pulmonary vascular development in bronchopulmonary dysplasia.Neonatology · 2015Review
- Ca(2+) and ion channels in hypoxia-mediated pulmonary hypertension.International journal of clinical and experimental pathology · 2015Review
- Role of reactive oxygen species in neonatal pulmonary vascular disease.Antioxidants & redox signaling · 2014Review
- The Robyn Barst Memorial Lecture: Differences between the fetal, newborn, and adult pulmonary circulations: relevance for age-specific therapies (2013 Grover Conference series).Pulmonary circulation · 2014Review
- Pulmonary Hypertension in Preterm Infants with Bronchopulmonary Dysplasia.Pediatric allergy, immunology, and pulmonology · 2014Review
- Endothelin-1 decreases endothelial PPARγ signaling and impairs angiogenesis after chronic intrauterine pulmonary hypertension.American journal of physiology. Lung cellular and molecular physiology · 2014Article
- A non-selective endothelin receptor antagonist bosentan modulates kinetics of bone marrow-derived cells in ameliorating pulmonary hypertension in mice.Pulmonary circulationArticle
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
backgroundEndothelin-1 (ET-1) and Rho-kinase (ROCK) increase vascular tone in experimental persistent pulmonary hypertension of the newborn (PPHN). Whether ET-1 activates ROCK to decrease angiogenesis in the developing lung remains unknown.
methodsProximal pulmonary artery endothelial cells (PAECs) were harvested from fetal sheep after partial ligation of the ductus arteriosus in utero (PPHN) and controls. Growth and tube formation were assessed after ET-1 treatment. The effect of ET-1 antagonism on tube formation was studied using ET-1 small interfering RNA (siRNA), ET-1 monoclonal antibodies (ET-1mAbs), BQ-123 (an ET(A) blocker), and bosentan (an ET(A)/ET(B) blocker). ET-1 gene and protein and ET(A)/ET(B) receptor protein expression were measured in normal and PPHN PAECs. ET-1-ROCK interactions were assessed by measuring ROCK activity after ET-1, ET-1 siRNA, and bosentan treatments, and tube formation with ET-1 and Y-27632 (ROCK inhibitor).
resultsET-1 did not affect growth but decreased tube formation in normal and PPHN PAECs. ET-1 protein and gene expression were increased and ET(B) receptor protein decreased in PPHN PAECs. ET-1 siRNA, ET-1mAbs, and bosentan, but not BQ-123, increased tube formation. ROCK activity was increased in PPHN PAECs and decreased with ET-1 siRNA and bosentan treatments. Y-27632 prevented the decrease in tube formation with ET-1.
conclusionET-1 activation of ROCK impairs angiogenesis of fetal PAECs. Disruption of ET-1-ROCK interactions may increase vascular growth in PPHN.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.