Nicotinamide benefits both mothers and pups in two contrasting mouse models of preeclampsia
| Autor: | Feng Li, Emiko Sato, Yuji Oe, Daisuke Saigusa, J. Charles Jennette, Hironobu Nakada, Sadayoshi Ito, Oliver Smithies, S. Ananth Karumanchi, H. W. Davin Townley-Tilson, John R. Hagaman, Nobuyuki Takahashi, Manyu Li, Akiyo Sekimoto, Tomofumi Fushima, Nobuyo Maeda, Hiroshi Sato, Gen Oyanagi, Jennifer Wilder |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Male
Niacinamide Vascular Endothelial Growth Factor A 0301 basic medicine medicine.medical_specialty Placenta Blood Pressure Suppressor of Cytokine Signaling Proteins 030204 cardiovascular system & hematology Biology Kidney Preeclampsia 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Pre-Eclampsia Pregnancy Internal medicine medicine Albuminuria Animals Receptor Placenta Growth Factor Fetus Fetal Growth Retardation Vascular Endothelial Growth Factor Receptor-1 Multidisciplinary Nicotinamide Body Weight Uterus Pregnancy Outcome Trophoblast Organ Size Biological Sciences medicine.disease Abortion Spontaneous Mice Inbred C57BL Vascular endothelial growth factor Disease Models Animal 030104 developmental biology Blood pressure medicine.anatomical_structure Endocrinology Animals Newborn chemistry Hypertension Embryo Loss Female Stem cell |
| DOI: | 10.17615/8m8h-9b59 |
| Popis: | Preeclampsia (PE) complicates ∼5% of human pregnancies and is one of the leading causes of pregnancy-related maternal deaths. The only definitive treatment, induced delivery, invariably results in prematurity, and in severe early-onset cases may lead to fetal death. Many currently available antihypertensive drugs are teratogenic and therefore precluded from use. Nonteratogenic antihypertensives help control maternal blood pressure in PE, but results in preventing preterm delivery and correcting fetal growth restriction (FGR) that also occurs in PE have been disappointing. Here we show that dietary nicotinamide, a nonteratogenic amide of vitamin B3, improves the maternal condition, prolongs pregnancies, and prevents FGR in two contrasting mouse models of PE. The first is caused by endotheliosis due to excess levels in the mothers of a soluble form of the receptor for vascular endothelial growth factor (VEGF), which binds to and inactivates VEGF. The second is caused by genetic absence of Ankiryn-repeat-and-SOCS-box–containing-protein 4, a factor that contributes to the differentiation of trophoblast stem cells into the giant trophoblast cells necessary for embryo implantation in mice; its absence leads to impaired placental development. In both models, fetal production of ATP is impaired and FGR is observed. We show here that nicotinamide decreases blood pressure and endotheliosis in the mothers, probably by inhibiting ADP ribosyl cyclase (ADPRC), and prevents FGR, probably by normalizing fetal ATP synthesis via the nucleotide salvage pathway. Because nicotinamide benefits both dams and pups, it merits evaluation for preventing or treating PE in humans. |
| Databáze: | OpenAIRE |
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