Language
English
Publication Date
12-1-2025
Journal
American Journal of Physiology: Lung Cellular and Molecular Physiology
DOI
10.1152/ajplung.00234.2025
PMID
41083253
PMCID
PMC12561899
PubMedCentral® Posted Date
10-29-2025
PubMedCentral® Full Text Version
Author MSS
Abstract
Bronchopulmonary dysplasia (BPD) associated pulmonary hypertension (PH) or BPD-PH is a lung disease of infants with significant morbidity. Adrenomedullin (Adm) is an angiogenic peptide that signals through calcitonin receptor-like receptor (Calcrl) and receptor activity modifying protein 2 (RAMP2). Adm deficiency potentiates hyperoxia-induced experimental BPD-PH in mice; however, whether Adm overexpression can mitigate this lung disease is unclear. Thus, we tested the hypothesis that Adm overexpression attenuates hyperoxia (HO)-induced murine experimental BPD-PH by using a novel transgenic mouse that overexpresses Adm globally (Admhi/hi mice). One-day-old Admhi/hi mice or their wild-type littermates (Adm+/+ mice) were exposed to HO (FiO2 70%) for 14 d and allowed to recover in normoxia (NO, FiO2 21%) for an additional 14 d. Controls were maintained in NO for 28 d. On postnatal day (P) 14, we harvested the lungs to determine the extent of Adm expression and apoptosis. On P28, we quantified alveolarization, lung vascularization, and PH. HO-exposed Adm+/+ mice demonstrated increased lung apoptosis, decreased alveolarization and lung vascularization, and indices of PH, indicating that neonatal HO exposure causes BPD-PH. However, Adm overexpression attenuated experimental BPD-PH, as evident by the decreased extent of hyperoxia-induced lung apoptosis and inflammation, alveolar and vascular simplification, pulmonary vascular remodeling, and PH in Admhi/hi mice than in Adm+/+ mice. Collectively, our results demonstrate that Adm overexpression attenuates HO-induced murine experimental BPD-PH, emphasizing the therapeutic potential of Adm for BPD-PH in preterm infants.
Keywords
Animals, Bronchopulmonary Dysplasia, Adrenomedullin, Hypertension, Pulmonary, Mice, Mice, Transgenic, Hyperoxia, Lung, Disease Models, Animal, Animals, Newborn, Humans, Adrenomedullin overexpression, mice, hyperoxia, bronchopulmonary dysplasia, pulmonary hypertension
Published Open-Access
yes
Recommended Citation
Thapa, Shyam; Sarkar, Poonam; Gaber, M Waleed; et al., "Adrenomedullin Overexpression Protects Mice From Experimental Bronchopulmonary Dysplasia and Associated Pulmonary Hypertension" (2025). Faculty and Staff Publications. 5959.
https://digitalcommons.library.tmc.edu/baylor_docs/5959