Michael W. Cookson, Tania Gonzalez, Elisa M. Bye, Greg Seedorf, Sarah Ellor, Brad J. Smith, James C. Fleet, Erica W. Mandell
University of Colorado, Anschutz School of Medicine and Children’s Hospital Colorado. University of Texas.
United States
American Journal of Physiology Lung Cellular and Molecular Physiology
Am J Physiol Lung Cell Mol Physiol 2025;
DOI: 10.1152/ajplung.00409.2024
Abstract
Preterm infants born to mothers with preeclampsia, a disease of vascular dysfunction, are at increased risk for bronchopulmonary dysplasia (BPD). Endothelial cells are critical in both maintaining proper vascular function and coordinating lung development. Understanding the mechanisms contributing to BPD in the setting of preeclampsia and how preeclampsia impacts pulmonary endothelial cells (PEC) in the newborn lung are required to decrease the burden of BPD. Vitamin D has been shown to improve lung angiogenesis and lung development in inflammatory models of BPD, but its therapeutic potential in the setting of preeclampsia is unknown. We hypothesized that intraamniotic (IA) treatment with the biologically active form of vitamin D, 1,25 dihydroxyvitamin D (1,25(OH)2D), will preserve lung growth in an experimental model of BPD induced by antenatal exposure to soluble VEGF receptor-1 (sFlt- 1[soluble fms-like tyrosine kinase 1]). Fetal rats were exposed to saline (control), sFlt-1 alone, 1,25(OH)2D alone, or simultaneous sFlt-1 + 1,25(OH)2D via IA injection during the late canalicular stage of lung development and delivered 2 days later. IA treatment with 1,25(OH)2D in sFlt-1 exposed pups improved lung alveolar and vascular growth and function at 14 days of life. PEC orchestrate alveolar development, and we demonstrate that IA sFlt-1 exposure alone decreased in vitro growth and tube formation of PEC isolated from newborn pups and that PEC from pups co-exposed to IA sFlt-1 and 1,25(OH)2D demonstrated increased growth and tube formation. We conclude that IA 1,25(OH)2D treatment improves distal lung development during sFlt-1 exposure through preservation of angiogenesis in the developing lung.
Category
Class III. Pulmonary Hypertension Associated with Lung Disease
Medical Therapy. Efficacy or Lack of Efficacy
Animal Models of Pulmonary Vascular Disease and Therapy
Vascular Cell Biology and Mechanisms of Pulmonary Vascular Disease
Age Focus: Pediatric Pulmonary Vascular Disease
Fresh or Filed Publication: Fresh (PHresh). Less than 1-2 years since publication
Article Access
Free PDF File or Full Text Article Available Through PubMed or DOI: Yes