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Possible Activation of the Renin-Angiotensin System in the Feto-Placental Unit in Preeclampsia

Department of Obstetrics and Gynecology (M.I., A.I., M.N., S.M.) and Laboratory of Molecular Pathogenesis (T.S.), Nagoya University School of Medicine; and Maternity and Perinatal Care Center (Y.O.) and Division of Pathology, Clinical Laboratory (T.N.), Nagoya University Hospital, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan

Address all correspondence and requests for reprints to: Atsuo Itakura, M.D., Department of Obstetrics and Gynecology, Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan. E-mail: . aita{at}med.nagoya-u.ac.jp

Abstract

The purpose of this study was to elucidate the mechanisms underlying the regulation of feto-placental circulation mediated by the renin-angiotensin system under preeclamptic conditions. We measured angiotensin-converting enzyme (ACE) activity, protein expression, and mRNA expression in uncomplicated and preeclamptic placentas and examined the localization of ACE. In addition, ACE activity and mRNA expression in human umbilical venous endothelial cells (HUVECs) under hypoxic conditions were analyzed. ACE activity, protein expression, and mRNA expression in placental tissues from preeclampsia were all significantly higher than those from uncomplicated pregnancies. ACE activity in vessel fractions was extensively higher than that in trophoblast-rich or macrophage-rich fractions. Additionally, ACE activity in HUVECs was significantly higher than that in human arterial endothelial cells, and ACE mRNA was primarily localized to venous endothelial cells of stem villous in placentas. Furthermore, hypoxic condition induced both ACE activity and mRNA expression in HUVECs. These results suggested that venous endothelial cells within placental stem villous tissues and umbilicus play an important role in the regulation of the feto-placental renin-angiotensin system, and in response to hypoxic conditions the feto-placental unit seemed to induce ACE activity in the placenta; such an effect would be likely to lead to regulation of the fetal circulation.

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