Simvastatin attenuates lung functional and vascular effects of hyperoxia in preterm rabbits

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dc.contributor.authorSalaets, Thomas
dc.contributor.authorTack, Bieke
dc.contributor.authorJiménez, Julio
dc.contributor.authorGie, Andrés
dc.contributor.authorLesage, Flore
dc.contributor.authorWinter, Derek
dc.contributor.authorBerghen, Nathalie
dc.contributor.authorAllegaert, Karel
dc.contributor.authorDeprest, Jan
dc.contributor.authorToelen, Jaan
dc.date.accessioned2020-08-31T19:48:46Z
dc.date.available2020-08-31T19:48:46Z
dc.date.issued2020-06
dc.description.abstractBackground: Bronchopulmonary dysplasia (BPD) remains a frequent complication following preterm birth, affecting respiratory health throughout life. Transcriptome analysis in a preterm rabbit model for BPD revealed dysregulation of key genes for inflammation, vascular growth and lung development in animals exposed to hyperoxia, which could be prevented by simvastatin. Methods: Preterm rabbits were randomized to either normoxia (21% O2) or hyperoxia (95% O2) and within each condition to treatment with 5 mg/kg simvastatin daily or control. Lung function, structure and mRNA-expression was assessed on day 7. Results: Simvastatin partially prevented the effect of hyperoxia on lung function, without altering alveolar structure or inflammation. A trend towards a less fibrotic phenotype was noted in simvastatin-treated pups, and airways were less muscularized. Most importantly, simvastatin completely prevented hyperoxia-induced arterial remodeling, in association with partial restoration of VEGFA and VEGF receptor 2 (VEGFR2) expression. Simvastatin however decreased survival in pups exposed to normoxia, but not to hyperoxia. Conclusion: Repurposing of simvastatin could be an advantageous therapeutic strategy for bronchopulmonary dysplasia and other developmental lung diseases with pulmonary vascular disease. The increased mortality in the treated normoxia group however limits the translational value at this dose and administration route.es
dc.identifier.citationPediatr Res . 2020 Jun;87(7):1193-1200. doi: 10.1038/s41390-019-0711-2es
dc.identifier.urihttps://doi.org/10.1038/s41390-019-0711-2es
dc.identifier.urihttp://hdl.handle.net/11447/3385
dc.language.isoenes
dc.publisherNature Pub Groupes
dc.subjectAnimalses
dc.subjectHyperoxiaes
dc.subjectLunges
dc.titleSimvastatin attenuates lung functional and vascular effects of hyperoxia in preterm rabbitses
dc.typeArticlees

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