Lack of EC-SOD worsens alveolar and vascular development in a neonatal mouse model of bleomycin-induced bronchopulmonary dysplasia and pulmonary hypertension

Pediatric Research
Cassidy DelaneyEva Nozik-Grayck

Abstract

Pulmonary hypertension (PH) worsens clinical outcomes in former preterm infants with bronchopulmonary dysplasia (BPD). Oxidant stress disrupts alveolar and vascular development in models of BPD. Bleomycin causes oxidative stress and induces BPD and PAH in neonatal rats. Disruption in the vascular endothelial growth factor (VEGF) and nitric oxide signaling pathways contributes to BPD. We hypothesized that loss of EC-SOD would worsen PAH associated with BPD in a neonatal mouse model of bleomycin-induced BPD by disrupting the VEGF/NO signaling pathway. Neonatal wild-type mice (WT), and mice lacking EC-SOD (EC-SOD KO) received intraperitoneal bleomycin (2 units/kg) or phosphate-buffered saline (PBS) three times weekly and were evaluated at weeks 3 or 4. Lack of EC-SOD impaired alveolar development and resulted in PH (elevated right ventricular systolic pressures, right ventricular hypertrophy (RVH)), decreased vessel density, and increased small vessel muscularization. Exposure to bleomycin further impaired alveolar development, worsened RVH and vascular remodeling. Lack of EC-SOD and bleomycin treatment decreased lung total and phosphorylated VEGFR2 and eNOS protein expression. EC-SOD is critical in preserving normal lung developm...Continue Reading

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Citations

Jun 1, 2016·Frontiers in Medicine·Cristina M Alvira
Jan 19, 2018·American Journal of Physiology. Lung Cellular and Molecular Physiology·Cassidy DelaneyEva Nozik-Grayck
Mar 13, 2020·Physiological Reports·Pavel Davizon-CastilloCassidy Delaney
Oct 4, 2017·American Journal of Physiology. Lung Cellular and Molecular Physiology·David E Surate SolaligueRory E Morty
Nov 15, 2019·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Nguyen Hoai NguyenCuong Thach Nguyen
Nov 21, 2018·Respiratory Research·Igor N ZelkoJesse Roman
Mar 28, 2019·Pediatric Pulmonology·Richard L Auten
Aug 29, 2020·International Journal of Molecular Sciences·Shih-Hsin Wang, Po-Nien Tsao
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Apr 30, 2019·Journal of the American Heart Association·Nguyen MaiMarc W Halterman
Nov 17, 2017·The Journal of Pediatrics·Cristina M Alvira, Rory E Morty
Dec 12, 2021·Molecular and Cellular Pediatrics·Mitali Sahni, Vineet Bhandari

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