Nitric oxide and reactive oxygen species in the pathogenesis of preeclampsia.
Preeclampsia (PE) is characterized by disturbed extravillous trophoblast migration toward uterine spiral arteries leading to increased uteroplacental vascular resistance and by vascular dysfunction resulting in reduced systemic vasodilatory properties. Its pathogenesis is mediated by an altered bioavailability of nitric oxide (NO) and tissue damage caused by increased levels of reactive oxygen species (ROS). Furthermore, superoxide (O2-) rapidly inactivates NO and forms peroxynitrite (ONOO-). It is known that ONOO- accumulates in the placental tissues and injures the placental function in PE. In addition, ROS could stimulate platelet adhesion and aggregation leading to intravascular coagulopathy. ROS-induced coagulopathy causes placental infarction and impairs the uteroplacental blood flow in PE. The disorders could lead to the reduction of oxygen and nutrients required for normal fetal development resulting in fetal growth restriction. On the other hand, several antioxidants scavenge ROS and protect tissues against oxidative damage. Placental antioxidants including catalase, superoxide dismutase (SOD), and glutathione peroxidase (GPx) protect the vasculature from ROS and maintain the vascular function. However, placental ischemia in PE decreases the antioxidant activity resulting in further elevated oxidative stress, which leads to the appearance of the pathological conditions of PE including hypertension and proteinuria. Oxidative stress is defined as an imbalance between ROS and antioxidant activity. This review provides new insights about roles of oxidative stress in the pathophysiology of PE.
Department of Obstetrics and Gynecology, Ehime University School of Medicine, Ehime 791-0295, Japan. keiichi@m.ehime-u.ac.jp.
Keiichi
K
Matsubara
Department of Pediatrics, Ehime University School of Medicine, Ehime 791-0295, Japan. higaki@m.ehime-u.ac.jp.
Takashi
T
Higaki
Department of Obstetrics and Gynecology, Ehime University School of Medicine, Ehime 791-0295, Japan. takeyu@m.ehime-u.ac.jp.
Yuko
Y
Matsubara
Department of Obstetrics and Gynecology, Ehime University School of Medicine, Ehime 791-0295, Japan. nawa2011@m.ehime-u.ac.jp.
Akihiro
A
Nawa
D000975:Antioxidants / Q000378:metabolism; D005260:Female; D006801:Humans; D008954:Models, Biological; D009569:Nitric Oxide / Q000378:metabolism*; D018384:Oxidative Stress; D010920:Placenta / Q000098:blood supply / Q000378:metabolism; D011225:Pre-Eclampsia / Q000378:metabolism*; D011247:Pregnancy; D017382:Reactive Oxygen Species / Q000378:metabolism*
D000975:Antioxidants; D017382:Reactive Oxygen Species; D009569:Nitric Oxide