Sildenafil Therapy Normalizes the Aberrant Metabolomic Profile in the Comt(-/-) Mouse Model of Preeclampsia/Fetal Growth Restriction
| Autor: | Joanna L. Stanley, Philip N. Baker, David S. Wishart, Rupasri Mandal, Sandra T. Davidge, Colin P. Sibley, Louise C. Kenny, David Broadhurst, Karolina Sulek, Irene J. Andersson |
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| Rok vydání: | 2015 |
| Předmět: |
medicine.medical_specialty
Sildenafil Catechol O-Methyltransferase Sildenafil Citrate Article Preeclampsia chemistry.chemical_compound Mice Metabolomics Pre-Eclampsia Pregnancy Internal medicine Medicine Animals Beta oxidation Mice Knockout Multidisciplinary Catechol-O-methyl transferase Fetal Growth Retardation biology business.industry medicine.disease Nitric oxide synthase Disease Models Animal Endocrinology chemistry Knockout mouse biology.protein Metabolome Female business |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | Preeclampsia (PE) and fetal growth restriction (FGR) are serious complications of pregnancy, associated with greatly increased risk of maternal and perinatal morbidity and mortality. These complications are difficult to diagnose and no curative treatments are available. We hypothesized that the metabolomic signature of two models of disease, catechol-O-methyl transferase (COMT−/−) and endothelial nitric oxide synthase (Nos3−/−) knockout mice, would be significantly different from control C57BL/6J mice. Further, we hypothesised that any differences in COMT−/− mice would be resolved following treatment with Sildenafil, a treatment which rescues fetal growth. Targeted, quantitative comparisons of serum metabolic profiles of pregnant Nos3−/−, COMT−/− and C57BL/6J mice were made using a kit from BIOCRATES. Significant differences in 4 metabolites were observed between Nos3−/− and C57BL/6J mice (p −/− mice (p −/− mice. Metabolomic profiling of mouse models is possible, producing signatures that are clearly different from control animals. A potential new treatment, Sildenafil, is able to normalize the aberrant metabolomic profile in COMT−/− mice; as this treatment moves into clinical trials, this information may assist in assessing possible mechanisms of action. |
| Databáze: | OpenAIRE |
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