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Ann Anat. 2014 Sep;196(5):268-77. doi: 10.1016/j.aanat.2014.04.002. Epub 2014 May 27.

A possible protective role of Nrf2 in preeclampsia.

Author information

1
Department of Anatomy and Cell Biology, Medical Faculty, RWTH Aachen University, Wendlingweg 2, 52074 Aachen, Germany. Electronic address: nkweider@ukaachen.de.
2
Institute of Cell Biology, Histology and Embryology, Center for Molecular Medicine, Medical University of Graz, Harrachgasse 21/7, 8010 Graz, Austria. Electronic address: berthold.huppertz@medunigraz.at.
3
Department of Anatomy and Cell Biology, Medical Faculty, RWTH Aachen University, Wendlingweg 2, 52074 Aachen, Germany; MEDIAN Kliniken, Baden-Württemberg, Germany. Electronic address: mkadyrov@ukaachen.de.
4
Obstetrics and Gynecology, Medical Faculty, University Hospital of the RWTH, Wendlingweg 2, 52074 Aachen, Germany. Electronic address: wrath@ukaachen.de.
5
Department of Anatomy and Cell Biology, Medical Faculty, RWTH Aachen University, Wendlingweg 2, 52074 Aachen, Germany. Electronic address: tpufe@ukaachen.de.
6
Department of Anatomy and Cell Biology, Medical Faculty, RWTH Aachen University, Wendlingweg 2, 52074 Aachen, Germany. Electronic address: cwruck@ukaachen.de.

Abstract

Excess release of reactive oxygen species (ROS) is a major cause of oxidative stress. This disturbance has been implicated as a cause of preeclampsia, a pregnancy-related disorder characterized by hypertension and proteinuria. Increased oxidative stress leads to trophoblast apoptosis/necrosis and alters the balance between pro- and anti-angiogenic factors, resulting in generalized maternal endothelial dysfunction. Trials using antioxidants have significantly failed to improve the condition of, or in any way protect, the mother from the life-threatening complications of this syndrome. Nuclear factor-erythroid 2-related factor 2 (Nrf2) is a potent transcription activator that regulates the expression of a multitude of genes that encode detoxification enzymes and anti-oxidative proteins. Recent discussion on evidence of a link between Nrf2 and vascular angiogenic balance has focussed on the downstream target protein, heme oxygenase-1 (HO-1). HO-1 metabolizes heme to biliverdin, iron and carbon monoxide (CO). HO-1/CO protects against hypertensive cardiovascular disease and contributes to the sustained health of the vascular system. In one animal model, sFlt-1 (soluble fms-like tyrosine kinase-1) has induced blood pressure elevation, but the induction of HO-1 attenuated the hypertensive response in the pregnant animals. The special conditions under which Nrf2 participates in the pathogenesis of preeclampsia are still unclear, as is whether Nrf2 attenuates or stimulates the processes involved in this syndrome. In this review, we summarize recent theories about how Nrf2 is involved in the pathogenesis of preeclampsia and present the reasons for considering Nrf2 as a therapeutic target for the treatment of preeclampsia.

KEYWORDS:

CO; Heme oxygenase-1; Nrf2; Preeclampsia

PMID:
24954650
DOI:
10.1016/j.aanat.2014.04.002
[Indexed for MEDLINE]

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