Nrf2 inactivation enhances placental angiogenesis in a preeclampsia mouse model and improves maternal and fetal outcomes

Science Signaling
Masahiro NezuMasayuki Yamamoto

Abstract

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.

References

Sep 1, 1992·Baillière's Clinical Obstetrics and Gynaecology·J N Bulmer
Apr 9, 1999·The Journal of Clinical Investigation·G WallukatF C Luft
Oct 29, 2000·Journal of the American Society of Nephrology : JASN·Jürgen BohlenderFriedrich C Luft
Jan 11, 2003·Journal of Obstetrics and Gynaecology : the Journal of the Institute of Obstetrics and Gynaecology·R MadazliN Tolun
May 2, 2003·Molecular Biotechnology·John E Hall
Oct 1, 2003·Nature Genetics·Nobunao WakabayashiMasayuki Yamamoto
Dec 23, 2003·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Tomoko SaitoAkiyoshi Fukamizu
Feb 7, 2004·Proceedings of the National Academy of Sciences of the United States of America·Nobunao WakabayashiPaul Talalay
Feb 7, 2004·The New England Journal of Medicine·Richard J LevineS Ananth Karumanchi
May 8, 2004·Expert Reviews in Molecular Medicine·Kristy Red-HorseSusan J Fisher
Apr 18, 2006·Lancet·L PostonUNKNOWN Vitamins in Pre-eclampsia (VIP) Trial Consortium
Jun 6, 2006·Nature Medicine·Shivalingappa VenkateshaS Ananth Karumanchi
Jun 20, 2006·Cardiovascular Research·Masuko Ushio-Fukai
Sep 8, 2006·The New England Journal of Medicine·Richard J LevineUNKNOWN CPEP Study Group
Oct 3, 2007·The Journal of Biological Chemistry·Md Ruhul AbidWilliam C Aird
Feb 13, 2008·Molecular and Cellular Biology·Tae YamamotoMasayuki Yamamoto
Feb 13, 2008·Laboratory Investigation; a Journal of Technical Methods and Pathology·Mitsuko FuruyaAkiyoshi Fukamizu
Mar 28, 2008·Current Hypertension Reports·Babbette D LaMarcaJoey P Granger
Apr 26, 2008·American Journal of Hypertension·Anne B WallisHani K Atrash
Aug 22, 2008·The New England Journal of Medicine·Bjørn Egil VikseBjarne M Iversen
Sep 2, 2008·Arteriosclerosis, Thrombosis, and Vascular Biology·Ellen C KeeleyRobert M Strieter
May 26, 2009·Seminars in Perinatology·Lelia Duley
Jul 21, 2009·Histopathology·Christoph Jan WruckMamed Kadyrov
Aug 25, 2009·Placenta·H ZhaoD K Stevenson
Mar 25, 2010·American Journal of Reproductive Immunology : AJRI·Christopher W G Redman, Ian L Sargent
Apr 9, 2010·The New England Journal of Medicine·James M RobertsUNKNOWN Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network
Apr 21, 2010·Molecular and Cellular Biology·Keiko TaguchiMasayuki Yamamoto
May 8, 2010·Arteriosclerosis, Thrombosis, and Vascular Biology·Sahoko IchiharaGaku Ichihara
Jul 6, 2010·Lancet·Eric A P SteegersRobert Pijnenborg
Oct 12, 2010·Nature·Aiwu ZhouRandy J Read
Oct 12, 2010·American Journal of Obstetrics and Gynecology·Mari LøsetRigmor Austgulen
Dec 29, 2010·Proceedings of the National Academy of Sciences of the United States of America·Keiichi KumasawaMasaru Okabe
May 27, 2011·Journal of Biochemistry·Junji IshidaAkiyoshi Fukamizu
Apr 26, 2012·Antioxidants & Redox Signaling·Aurelie Nguyen Dinh CatRhian M Touyz

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Citations

Apr 28, 2019·The Journal of Physiological Sciences : JPS·Eriko Takimoto-Ohnishi, Kazuo Murakami
Aug 24, 2017·American Journal of Hypertension·Undurti N Das
Aug 31, 2019·Clinical and Experimental Pharmacology & Physiology·Joshua J FisherOlivia J Holland
Apr 27, 2020·Journal of Tissue Engineering and Regenerative Medicine·Zi Guo, Zhaohui Mo
Nov 14, 2019·BMC Genomics·Jennifer N KiserHolly L Neibergs
Mar 15, 2018·Indian Journal of Pediatrics·Shikha Rani, Deepak Chawla
Aug 27, 2017·The Journal of Biological Chemistry·Takafumi Suzuki, Masayuki Yamamoto
May 5, 2018·American Journal of Reproductive Immunology : AJRI·Wendy FitzgeraldLeonid Margolis
Nov 21, 2018·Cell Death & Disease·Olivia J HollandAnthony V Perkins
Aug 3, 2019·Archives of Pharmacal Research·Cody J SchmidlinDonna D Zhang
Apr 25, 2019·Current Medical Science·Jian-Li WuLing Feng
Mar 30, 2021·ACS Applied Materials & Interfaces·Andrew W PhillipsBozhi Tian
Sep 2, 2021·American Journal of Reproductive Immunology : AJRI·Ourlad Alzeus G TantengcoRamkumar Menon
May 18, 2017·Science Signaling·Wei Wong

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