title: Artificial oxygen carriers rescue placental hypoxia and improve fetal development in the rat pre-eclampsia model.
abstract: Pre-eclampsia affects approximately 5% of all pregnant women and remains a major cause of maternal and fetal morbidity and mortality. The hypertension associated with pre-eclampsia develops during pregnancy and remits after delivery, suggesting that the placenta is the most likely origin of this disease. The pathophysiology involves insufficient trophoblast invasion, resulting in incomplete narrow placental spiral artery remodeling. Placental insufficiency, which limits the maternal-fetal exchange of gas and nutrients, leads to fetal intrauterine growth restriction. In this study, in our attempt to develop a new therapy for pre-eclampsia, we directly rescued placental and fetal hypoxia with nano-scale size artificial oxygen carriers (hemoglobin vesicles). The present study is the first to demonstrate that artificial oxygen carriers successfully treat placental hypoxia, decrease maternal plasma levels of anti-angiogenic proteins and ameliorate fetal growth restriction in the pre-eclampsia rat model.
authors.affiliation: Department of Developmental Disorders, National Institute of Mental Health, National Center of Neurology and Psychiatry, Kodira, Tokyo, Japan.
authors.forename: Heng
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Developmental Disorders, National Institute of Mental Health, National Center of Neurology and Psychiatry, Kodira, Tokyo, Japan.
authors.forename: Hidenobu
authors.initials: H
authors.lastname: Ohta
authors.affiliation: Center for Advanced Biomedical Sciences, Waseda University, Shinjuku-ku, Tokyo, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Tahara
authors.affiliation: Image Processing Research Team, RIKEN Center for Advanced Photonics, RIKEN, Wako, Saitama, Japan.
authors.forename: Sakiko
authors.initials: S
authors.lastname: Nakamura
authors.affiliation: Faculty of Pharmaceutical Sciences, Sojo University, Kumamoto, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Taguchi
authors.affiliation: Department of Developmental Disorders, National Institute of Mental Health, National Center of Neurology and Psychiatry, Kodira, Tokyo, Japan.|Department of Pediatrics, St. Luke's International Hospital, Chuo-ku, Tokyo, Japan.
authors.forename: Machiko
authors.initials: M
authors.lastname: Nakagawa
authors.affiliation: Department of Developmental Disorders, National Institute of Mental Health, National Center of Neurology and Psychiatry, Kodira, Tokyo, Japan.|Department of Pediatrics, Japanese Red Cross Medical Center, Tokyo, Japan.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Oishi
authors.affiliation: Department of Mental Retardation and Birth Defect Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan.
authors.forename: Yu-Ichi
authors.initials: Y
authors.lastname: Goto
authors.affiliation: Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Wada
authors.affiliation: Department of Developmental Disorders, National Institute of Mental Health, National Center of Neurology and Psychiatry, Kodira, Tokyo, Japan.
authors.forename: Makiko
authors.initials: M
authors.lastname: Kaga
authors.affiliation: Department of Developmental Disorders, National Institute of Mental Health, National Center of Neurology and Psychiatry, Kodira, Tokyo, Japan.
authors.forename: Masumi
authors.initials: M
authors.lastname: Inagaki
authors.affiliation: Faculty of Pharmaceutical Sciences, Sojo University, Kumamoto, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Otagiri
authors.affiliation: Image Processing Research Team, RIKEN Center for Advanced Photonics, RIKEN, Wako, Saitama, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Yokota
authors.affiliation: Center for Advanced Biomedical Sciences, Waseda University, Shinjuku-ku, Tokyo, Japan.
authors.forename: Shigenobu
authors.initials: S
authors.lastname: Shibata
authors.affiliation: Department of Chemistry, Faculty of Medicine, School of Medicine, Nara Medical University, Kashihara, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Sakai
authors.affiliation: Department of Obstetrics and Gynecology, Tohoku University Hospital, Aoba-ku, Sendai, Japan.
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Okamura
authors.affiliation: Department of Obstetrics and Gynecology, Tohoku University Hospital, Aoba-ku, Sendai, Japan.
authors.forename: Nobuo
authors.initials: N
authors.lastname: Yaegashi
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001802:Blood Substitutes / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D001921:Brain / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D000071063:Endoglin; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D047109:Fetal Development / Q000187:drug effects*; D006801:Humans; D000860:Hypoxia; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000097:blood; D008163:Luminescent Measurements; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D049329:Nanostructures / Q000737:chemistry; D010920:Placenta / Q000378:metabolism* / Q000473:pathology; D011225:Pre-Eclampsia / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood
chemical_list: D001802:Blood Substitutes; D000071063:Endoglin; C501740:Eng protein, rat; D047908:Intracellular Signaling Peptides and Proteins; C501164:Flt1 protein, rat; D040281:Vascular Endothelial Growth Factor Receptor-1; D019331:NG-Nitroarginine Methyl Ester