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

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dc.contributor.author Salaets, Thomas
dc.contributor.author Tack, Bieke
dc.contributor.author Jiménez, Julio
dc.contributor.author Gie, Andrés
dc.contributor.author Lesage, Flore
dc.contributor.author Winter, Derek
dc.contributor.author Berghen, Nathalie
dc.contributor.author Allegaert, Karel
dc.contributor.author Deprest, Jan
dc.contributor.author Toelen, Jaan
dc.date.accessioned 2020-08-31T19:48:46Z
dc.date.available 2020-08-31T19:48:46Z
dc.date.issued 2020-06
dc.identifier.citation Pediatr Res . 2020 Jun;87(7):1193-1200. doi: 10.1038/s41390-019-0711-2 es
dc.identifier.uri https://doi.org/10.1038/s41390-019-0711-2 es
dc.identifier.uri http://hdl.handle.net/11447/3385
dc.description.abstract Background: 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.language.iso en es
dc.publisher Nature Pub Group es
dc.subject Animals es
dc.subject Hyperoxia es
dc.subject Lung es
dc.title Simvastatin attenuates lung functional and vascular effects of hyperoxia in preterm rabbits es
dc.type Article es


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