Xueyu Chen, Dongshan Han, Xuan Wang, Xuemei Huang, Zilu Huang, Yijun Liu, Junyan Zhong, Frans J. Walther, Chuanzhong Yang, Gerry T. M. Wagenaar
Affiliated Shenzhen Maternity and Child Healthcare Hospital, The First School of Clinical Medicine, Southern Medical University. David Geffen School of Medicine, University of California Los Angeles. Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center. VU University Amsterdam.
China, United States and Netherlands
Respiratory Research
Respir Res 2023; 24:
DOI: 10.1186/s12931-023-02342-4
Abstract
Background: Ibuprofen is a nonsteroidal anti-inflammatory drug that is commonly used to stimulate closure of a patent ductus arteriosus (PDA) in very premature infants and may lead to aberrant neonatal lung development and bronchopulmonary dysplasia (BPD).
Methods: We investigated the effect of ibuprofen on angiogenesis in human umbilical cord vein endothelial cells (HUVECs) and the therapeutic potential of daily treatment with 50 mg/kg of ibuprofen injected subcutaneously in neonatal Wistar rat pups with severe hyperoxia-induced experimental BPD. Parameters investigated included growth, survival, lung histopathology and mRNA expression.
Results: Ibuprofen inhibited angiogenesis in HUVECs, as shown by reduced tube formation, migration and cell proliferation via inhibition of the cell cycle S-phase and promotion of apoptosis. Treatment of newborn rat pups with ibuprofen reduced pulmonary vessel density in the developing lung, but also attenuated experimental BPD by reducing lung inflammation, alveolar enlargement, alveolar septum thickness and small arteriolar wall thickening.
Conclusions: In conclusion, ibuprofen has dual effects on lung development: adverse effects on angiogenesis and beneficial effects on alveolarization and inflammation. Therefore, extrapolation of the beneficial effects of ibuprofen to premature infants with BPD should be done with extreme caution.
Category
Animal Models of Pulmonary Vascular Disease and Therapy
Class III. Pulmonary Hypertension Associated with Lung Disease
Class I. Drug-induced and Toxin-induced Pulmonary Hypertensio
Age Focus: Pediatric Pulmonary Vascular Disease
Fresh or Filed Publication: Filed (PHiled). Greater than 1-2 years since publication
Article Access
Free PDF File or Full Text Article Available Through PubMed or DOI: Yes