Chorioamnionitis is associated with preterm delivery and bronchopulmonary dysplasia (BPD), characterized by impaired alveolar and pulmonary vascular development and vascular dysfunction. To study the vascular effects in a model of chorioamnionitis, preterm lambs were exposed to 20 mg of intra-amniotic endotoxin or saline for 1, 2, 4, or 7 days and delivered at 122 days gestational age (term = 150 days). This intra-amniotic endotoxin dose was previously shown to induce lung maturation. The effect of intra-amniotic endotoxin on expression of endothelial proteins was evaluated. Muscularization of the media and collagen deposition in adventitia of small pulmonary arteries was used to assess vascular remodeling. Compared with controls, bronchoalveolar lavage fluid protein content was increased 2 days after intra-amniotic endotoxin exposure. Vascular endothelial growth factor (VEGF) 165 isoform mRNA decreased 2-4 days after intra-amniotic endotoxin. VEGF, VEGF receptor-2, endothelial nitric oxide synthase (eNOS), platelet endothelial cell adhesion molecule-1, and Tie-2 protein expression in the lung coordinately decreased 1-7 days after intra-amniotic endotoxin. Intra-amniotic endotoxin appeared to selectively decrease eNOS expression in small pulmonary vessels compared with large vessels. Medial smooth muscle hypertrophy and increased adventitial fibrosis were observed 4 and 7 days after intra-amniotic endotoxin. These results demonstrate that, in the preterm lamb lung, antenatal inflammation inhibits endothelial cell protein expression followed by vascular remodeling changes in small pulmonary arteries. Exposure to antenatal inflammation may cause vascular remodeling and contribute to the development of BPD.
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http://dx.doi.org/10.1152/ajplung.00049.2004 | DOI Listing |
J Matern Fetal Neonatal Med
December 2025
Neonatal Intensive Care Unit, G d'Annunzio University of Chieti, Italy.
Background: Adrenomedullin (AM) is a potent angiogenic, antioxidant and anti-inflammatory peptide protecting the developing lung from injury due to bronchopulmonary dysplasia (BPD) of the preterm infant. At this stage, no data on the potential effects of chorioamnionitis (CA) occurrence and glucocorticoids (GC) administration on AM in developing lungs are still lacking.
Objective: to investigate, in a sheep-based model, the positive/side-effects of combined exposure to CA and GC on AM concentrations measured in bronchoalveolar lavage fluid (BALF).
Am J Physiol Lung Cell Mol Physiol
January 2025
Department of Pediatrics, Boston Medical Center, Boston University Chobanian and Avedisian School of Medicine, Boston, Massachusetts, United States.
Intrauterine inflammation from chorioamnionitis (CA) is associated with placental dysfunction and increased risk of bronchopulmonary dysplasia (BPD), the chronic lung disease of prematurity. Antenatal steroid (ANS) treatment improves early respiratory outcomes for premature infants. However, it remains unclear whether ANS improves long-term respiratory outcomes, and whether these effects are mediated through the improvement of placental dysfunction and/or direct impact on the fetal lung.
View Article and Find Full Text PDFFront Pediatr
September 2024
Animal Research Unit, Biocruces-Bizkaia Health Research Institute, Barakaldo, Spain.
Pediatr Pulmonol
December 2024
Department of Pediatrics, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Objectives: Bronchopulmonary dysplasia (BPD), the most common late morbidity in preterm infants, is characterized by impaired alveolar development caused by persistent lung inflammation. Studies have shown that NOD-, LRR- and pyrin domain-containing 3 (NLRP3) inflammasome-mediated inflammation is critically involved in the development of BPD. As a traditional Chinese medicinal herb, Eclipta prostrata (EAP) exhibits potent anti-inflammatory properties.
View Article and Find Full Text PDFAJOG Glob Rep
August 2024
Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Madigan Army Medical Center, Tacoma, WA (Leonard, Schmiedecke, Walton, and Ieronimakis).
Background: Preterm birth from intrauterine infection is a leading cause of neonatal neurologic morbidity. Likewise, maternal obesity is associated with intra-amniotic infection and inflammation. Whether maternal obesity is a risk factor for fetal brain injury that occurs with premature birth remains unknown.
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