ArticleAmerican journal of physiology. Lung cellular and molecular physiology2015
Prevention of pulmonary hypoplasia and pulmonary vascular remodeling by antenatal simvastatin treatment in nitrofen-induced congenital diaphragmatic hernia.
Article in American journal of physiology. Lung cellular and molecular physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- Pulmonary hypertension secondary to congenital diaphragmatic hernia: factors and pathways involved in pulmonary vascular remodeling.Pediatric research · 2019Pooled it
- Antenatal Sildenafil for Congenital Diaphragmatic Hernia: A Systematic Review and Bayesian Meta-Analysis of Preclinical Studies.Biomedicines · 2025Review
- The nitrofen/bisdiamine murine model of congenital diaphragmatic hernia has a pulmonary hypertension vascular phenotype consistent with human CDH.American journal of physiology. Lung cellular and molecular physiology · 2025Article
- Early Alteration of Right Ventricle-Pulmonary Artery Coupling in Experimental Heart Failure With Preserved Ejection Fraction.Journal of the American Heart Association · 2024Article
- Early diagnosis and targeted approaches to pulmonary vascular disease in bronchopulmonary dysplasia.Pediatric research · 2022Review
- Association of asymmetric dimethylarginine with the pathological process of persistent pulmonary hypertension of the newborn.Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2022Article
- Emerging antenatal therapies for congenital diaphragmatic hernia-induced pulmonary hypertension in preclinical models.Pediatric research · 2021Review
- ROBO2 signaling in lung development regulates SOX2/SOX9 balance, branching morphogenesis and is dysregulated in nitrofen-induced congenital diaphragmatic hernia.Respiratory research · 2020Article
- Simvastatin attenuates lung functional and vascular effects of hyperoxia in preterm rabbits.Pediatric research · 2020Article
- Decreased OLA1 (Obg-Like ATPase-1) Expression Drives Ubiquitin-Proteasome Pathways to Downregulate Mitochondrial SOD2 (Superoxide Dismutase) in Persistent Pulmonary Hypertension of the Newborn.Hypertension (Dallas, Tex. : 1979) · 2019Article
- MIF inhibition enhances pulmonary angiogenesis and lung development in congenital diaphragmatic hernia.Pediatric research · 2019Article
- The proportion of alveolar type 1 cells decreases in murine hypoplastic congenital diaphragmatic hernia lungs.PloS one · 2019Article
- Intra-amniotic Sildenafil Treatment Modulates Vascular Smooth Muscle Cell Phenotype in the Nitrofen Model of Congenital Diaphragmatic Hernia.Scientific reports · 2018Article
- Pulmonary vascular development in congenital diaphragmatic hernia.European respiratory review : an official journal of the European Respiratory Society · 2018Review
- Changes in vasoactive pathways in congenital diaphragmatic hernia associated pulmonary hypertension explain unresponsiveness to pharmacotherapy.Respiratory research · 2017Article
- Update on novel targets and potential treatment avenues in pulmonary hypertension.American journal of physiology. Lung cellular and molecular physiology · 2016Review
- Polygenic Causes of Congenital Diaphragmatic Hernia Produce Common Lung Pathologies.The American journal of pathology · 2016Review
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Congenital diaphragmatic hernia (CDH) has a high mortality rate mainly due to lung hypoplasia and persistent pulmonary hypertension of the newborn (PPHN). Simvastatin has been shown to prevent the development of pulmonary hypertension (PH) in experimental models of PH. We, therefore, hypothesized that antenatal simvastatin would attenuate PPHN in nitrofen-induced CDH in rats. The efficacy of antenatal simvastatin was compared with antenatal sildenafil, which has already been shown to improve pathological features of PPHN in nitrofen-induced CDH. On embryonic day (E) 9.5, nitrofen or vehicle was administered to pregnant Sprague-Dawley rats. On E11, nitrofen-treated rats were randomly assigned to antenatal simvastatin (20 mg·kg(-1)·day(-1) orally), antenatal sildenafil (100 mg·kg(-1)·day(-1) orally), or placebo administration from E11 to E21. On E21, fetuses were delivered by cesarean section, killed, and checked for left-sided CDH. Lung tissue was then harvested for further pathobiological evaluation. In nitrofen-induced CDH, simvastatin failed to reduce the incidence of nitrofen-induced CDH in the offspring and to increase the body weight, but improved the lung-to-body weight ratio and lung parenchyma structure. Antenatal simvastatin restored the pulmonary vessel density and external diameter, and reduced the pulmonary arteriolar remodeling compared with nitrofen-induced CDH. This was associated with decreased lung expression of endothelin precursor, endothelin type A and B receptors, endothelial and inducible nitric oxide synthase, together with restored lung activation of apoptotic processes mainly in the epithelium. Antenatal simvastatin presented similar effects as antenatal therapy with sildenafil on nitrofen-induced CDH. Antenatal simvastatin improves pathological features of lung hypoplasia and PPHN in experimental nitrofen-induced CDH.
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