Caffeine is associated with improved alveolarization and angiogenesis in male mice following hyperoxia induced lung injury

BMC Pulmonary Medicine
Vikramaditya DumpaVasantha H S Kumar

Abstract

Caffeine therapy for apnea of prematurity reduces the incidence of bronchopulmonary dysplasia (BPD) in premature neonates. Several mechanisms, including improvement in pulmonary mechanics underly beneficial effects of caffeine in BPD. As vascular development promotes alveologenesis, we hypothesized that caffeine might enhance angiogenesis in the lung, promoting lung growth, thereby attenuating BPD. C57Bl/6 mice litters were randomized within 12 h of birth to room air (RA) or 95%O2 to receive caffeine (20 mg/kg/day) or placebo for 4 days and recovered in RA for 12wks. The lung mRNA and protein expression for hypoxia-inducible factors (HIF) and angiogenic genes performed on day 5. Lung morphometry and vascular remodeling assessed on inflation fixed lungs at 12wks. Caffeine and hyperoxia in itself upregulate HIF-2α and vascular endothelial growth factor gene expression. Protein expression of HIF-2α and VEGFR1 were higher in hyperoxia/caffeine and angiopoietin-1 lower in hyperoxia. An increase in radial alveolar count, secondary septal count, and septal length with a decrease in mean linear intercept indicate an amelioration of hyperoxic lung injury by caffeine. An increase in vessel surface area and a significant reduction in smoo...Continue Reading

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Citations

Oct 28, 2019·Children·Vasantha H S Kumar, Steven E Lipshultz
May 24, 2020·Journal of Clinical Medicine·Luca BonadiesEugenio Baraldi
Oct 10, 2019·American Journal of Physiology. Lung Cellular and Molecular Physiology·Ettore LignelliRory E Morty
Jun 26, 2021·Frontiers in Pediatrics·Gergely ToldiThillagavathie Pillay
Jun 3, 2020·American Journal of Perinatology·Ajay Pratap SinghVasantha H S Kumar

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