Journal
SCIENCE SIGNALING
Volume 10, Issue 479, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/scisignal.aam5711
Keywords
-
Categories
Funding
- Ministry of Education, Culture, Sports, Science and Technology/Japan Society for the Promotion of Science KAKENHI [24249015, 26111002, 26116702, 15H04691, 12J07924]
- Core Research for Evolutional Science and Technology from the Japan Agency for Medical Research and Development
- Sakakibara Memorial Research Grant from the Japan Research Promotion Society for Cardiovascular Diseases
- Grants-in-Aid for Scientific Research [12J07924, 26116702, 15H04691, 17K19680, 17H01519, 26111002] Funding Source: KAKEN
Ask authors/readers for more resources
Placental activation of the renin-angiotensin system (RAS) plays a key role in the pathogenesis of preeclampsia. Reactive oxygen species (ROS) are thought to affect placental angiogenesis, which is critical for preventing preeclampsia pathology. We examined the role of ROS in preeclampsia by genetically modifying the Keap1-Nrf2 pathway, a cellular antioxidant defense system, in a mouse model of RAS-induced preeclampsia. Nrf2 deficiency would be expected to impair cellular antioxidant responses; however, Nrf2 deficiency in preeclamptic mice improved maternal and fetal survival, ameliorated intra-uterine growth retardation, and augmented oxidative DNA damage. Furthermore, the placentas of Nrf2-deficient mice had increased endothelial cell proliferation with dense vascular networks. In contrast, the placentas of preeclamptic mice with overactive Nrf2 showed repressed angiogenesis, which was associated with decreased expression of genes encoding angiogenic chemokines and cytokines. Our findings support the notion that ROS-mediated signaling is essential for maintaining placental angiogenesis in preeclampsia and may provide mechanistic insight into the negative results of clinical trials for antioxidants in preeclampsia.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available