Excessive autophagy induces the failure of trophoblast invasion and vasculature:Possible relevance to the pathogenesis of preeclampsia

Gaoa, Li, Qi, Hong Bo, Kc, Kamana, Zhang, Xue Mei, Zhang, Hua and Baker, Philip N. (2015) Excessive autophagy induces the failure of trophoblast invasion and vasculature:Possible relevance to the pathogenesis of preeclampsia. Journal of Hypertension, 33 (1). pp. 106-117. ISSN 0263-6352

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Abstract

Introduction: Preeclampsia affects 5-7% of all healthy pregnancies and is characterized by hypertension and proteinuria. Although the pathogenesis of preeclampsia is still not fully understood, a failure of spiral artery transformation and aberrant placental vasculature are considered to be facets of this disease. Studies have also implicated increased autophagic activity. In this study, we investigated whether oxidative stress could increase autophagic activity and consequently affect trophoblast invasion and the placental vasculature. Methods: Placentas from 18 pregnancies complicated by preeclampsia and from 18 uncomplicated pregnancies, trophoblast HTR8/SVneo cell line (HTR8/SVneo) extravillous trophoblasts, and human umbilical vein endothelial cells (HUVECs) were employed. The levels of autophagy markers LC3, Beclin-1 and autophagosome were quantified by immunohistochemistry, Western blotting and RT-PCR in placental tissue, and in trophoblasts and endothelial cells that had been treated with an oxidative stress inducer glucose oxidase. Trophoblast invasion and endothelial cell tube formation were assessed in HTR8/SVneo cells or HUVECs that had been treated with glucose oxidase. Results: The expression of LC3, Beclin-1 and autophagosome was significantly increased in placentas from pregnancies complicated by early-onset preeclampsia and in HTR8/SVneo cells and HUVECs treated with glucose oxidase. In addition, trophoblast invasion and endothelial cell tube formation were significantly reduced in HTR8/ SVneo cells or HUVECs that had been treated with glucose oxidase. Conclusion: Our data suggest that oxidative stress induces increased autophagy in trophoblasts or endothelial cells which affects trophoblast invasion and the placental vasculature. Excessive autophagic activity may be involved in the development of preeclampsia.

Item Type: Article
Additional Information: Publisher Copyright: © 2014 Wolters Kluwer Health.
Uncontrolled Keywords: autophagy,endothelial tube formation,oxidative stress,preeclampsia,trophoblast invasion,internal medicine,physiology,cardiology and cardiovascular medicine ,/dk/atira/pure/subjectarea/asjc/2700/2724
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups: Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health
Related URLs:
Depositing User: LivePure Connector
Date Deposited: 27 Feb 2026 10:30
Last Modified: 27 Feb 2026 10:30
URI: https://ueaeprints.uea.ac.uk/id/eprint/102093
DOI: 10.1097/HJH.0000000000000366

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