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rhIGF-1 Therapy: A Silver Bullet for Bronchopulmonary Dysplasia Prevention?
- Source :
- American Journal of Respiratory and Critical Care Medicine
- Publication Year :
- 2020
- Publisher :
- American Thoracic Society, 2020.
-
Abstract
- Rationale: Antenatal factors, such as chorioamnionitis, preeclampsia, and postnatal injury, are associated with an increased risk for bronchopulmonary dysplasia (BPD) and pulmonary hypertension (PH) after preterm birth. IGF-1 (insulin-like growth factor-1) is markedly decreased in normal preterm infants, but whether IGF-1 treatment can prevent BPD or PH is unknown. Objectives: To evaluate whether postnatal treatment with rhIGF-1 (recombinant human IGF-1)/BP3 (binding peptide 3) improves lung growth and prevents PH in two antenatal models of BPD induced by intraamniotic exposure to endotoxin (ETX) or sFlt-1 (soluble fms-like tyrosine kinase 1), and in a postnatal model due to prolonged hyperoxia. Methods: ETX or sFlt-1 were administered into the amniotic sac of pregnant rats at Embryonic Day 20 to simulate antenatal models of chorioamnionitis and preeclampsia, respectively. Pups were delivered by cesarean section at Embryonic Day 22 and treated with rhIGF-1/BP3 (0.02–20 mg/kg/d intraperitoneal) or buffer for 2 weeks. Study endpoints included radial alveolar counts (RACs), vessel density, and right ventricular hypertrophy (RVH). Direct effects of rhIGF-1/BP3 (250 ng/ml) on fetal lung endothelial cell proliferation and tube formation and alveolar type 2 cell proliferation were studied by standard methods in vitro. Measurements and Main Results: Antenatal ETX and antenatal sFlt-1 reduced RAC and decreased RVH in infant rats. In both models, postnatal rhIGF-1/BP3 treatment restored RAC and RVH to normal values when compared with placebo injections. rhIGF-1/BP3 treatment also preserved lung structure and prevented RVH after postnatal hyperoxia. In vitro studies showed that rhIGF-1/BP3 treatment increased lung endothelial cell and alveolar type 2 cell proliferation. Conclusions: Postnatal rhIGF-1/BP3 treatment preserved lung structure and prevented RVH in antenatal and postnatal BPD models. rhIGF-1/BP3 treatment may provide a novel strategy for the prevention of BPD in preterm infants.
- Subjects :
- Pulmonary and Respiratory Medicine
Male
Postnatal Care
medicine.medical_specialty
Hypertension, Pulmonary
Critical Care and Intensive Care Medicine
Rats, Sprague-Dawley
angiogenesis
Pregnancy
pulmonary hypertension
medicine
Animals
Humans
Insulin-Like Growth Factor I
Lung
lung development
Bronchopulmonary Dysplasia
business.industry
prematurity
Editorials
Infant, Newborn
Infant
Original Articles
Pediatrics and Lung Development/Pulmonary Vascular Disease
medicine.disease
Surgery
Rats
insulin-like growth factor-1
Bronchopulmonary dysplasia
Silver bullet
Animals, Newborn
Models, Animal
Female
business
Infant, Premature
Subjects
Details
- Language :
- English
- ISSN :
- 15354970 and 1073449X
- Volume :
- 201
- Issue :
- 9
- Database :
- OpenAIRE
- Journal :
- American Journal of Respiratory and Critical Care Medicine
- Accession number :
- edsair.doi.dedup.....6dabea3c55d72b61837e9250b48590d6