Translatable mitochondria-targeted protection against programmed cardiovascular dysfunction
| Autor: | Michael P. Murphy, Nozomi Itani, Katie L. Skeffington, Youguo Niu, Christian Beck, Dino A. Giussani, A. J. Murray, Kimberley J. Botting, Beth J. Allison, Kirsty L. Brain, Angela Logan |
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| Rok vydání: | 2020 |
| Předmět: |
Heart disease
Offspring Placenta Chick Embryo Bioinformatics medicine.disease_cause Antioxidants 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine In vivo Pregnancy Medicine Animals Endothelial dysfunction Hypoxia Research Articles 030304 developmental biology 0303 health sciences Fetus MitoQ Multidisciplinary Sheep business.industry SciAdv r-articles Hypoxia (medical) medicine.disease Mitochondria chemistry Female medicine.symptom business Chickens 030217 neurology & neurosurgery Oxidative stress Research Article Developmental Biology |
| Zdroj: | Science Advances |
| ISSN: | 2375-2548 |
| Popis: | Mitochondrial therapy may cure hypertension in adult offspring of complicated pregnancies. The prenatal origins of heart disease in offspring have been established. However, research in species with developmental milestones comparable to humans is lacking, preventing translation of this knowledge to clinical contexts. Using sheep and chickens, two species with similar cardiovascular developmental milestones to humans, we combined in vivo experiments with in vitro studies at organ, cellular, mitochondrial, and molecular levels. We tested mitochondria-targeted antioxidant intervention with MitoQ against cardiovascular dysfunction programmed by developmental hypoxia, a common complication in human pregnancy. Experiments in sheep determined in vivo fetal and adult cardiovascular function through surgical techniques not possible in humans, while those in chicken embryos isolated effects independent of maternal or placental influences. We show that hypoxia generates mitochondria-derived oxidative stress during cardiovascular development, programming endothelial dysfunction and hypertension in adult offspring. MitoQ treatment during hypoxic development protects against this cardiovascular risk via enhanced nitric oxide signaling, offering a plausible intervention strategy. |
| Databáze: | OpenAIRE |
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