Dépôt numérique

Galectin-7 dysregulates renin-angiotensin-aldosterone and NADPH oxide synthase pathways in preeclampsia

Menkhorst, Ellen; Zhou, Wei; Santos, Leilani; Zhang, Jian-Guo; St-Pierre, Yves ORCID logoORCID: https://orcid.org/0000-0002-1948-2041; Young, Morag J et Dimitriadis, Evdokia (2022). Galectin-7 dysregulates renin-angiotensin-aldosterone and NADPH oxide synthase pathways in preeclampsia Pregnancy Hypertension , vol. 30 . pp. 130-136. DOI: 10.1016/j.preghy.2022.09.008.

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OBJECTIVES: Preeclampsia is a life-threatening disorder of pregnancy unique to humans. Poor placentation in the first trimester of pregnancy is widely accepted to be an underlying cause of preeclampsia. Galectin-7 is abnormally elevated in chorionic villous samples and serum from women that subsequently develop pre-term preeclampsia. Administration of exogenous galectin-7 to pregnant mice causes preeclampsia-like features (hypertension, proteinuria), associated with dysregulation of the renin-angiotensin system (RAS). In this study investigated the mechanism by which galectin-7 induces alterations to tissue RAS homeostasis and ROS production. We hypothesized that galectin-7 induces alterations in the production of either placental RAS or NADPH oxidases (or both) to drive the dysregulated RAS and ROS production seen in preeclampsia. STUDY DESIGN: Mated female mice (n = 5-6/group) received single (embryonic day [E]12/13) or multiple (E8-12) subcutaneous injections of 400 μg/kg/day galectin-7 or vehicle control and killed on E13 or E18. Human first trimester placental villous and decidual tissue (n = 11) was cultured under 8 % oxygen with 1 µg/mL galectin-7 or vehicle control for 16 h. RESULTS: Galectin-7 administration to pregnant mice impaired placental labyrinth formation, suppressed circulating aldosterone and altered placental RAS (Agt, Renin) and NADPH oxidase (Cyba, Cybb and Icam1) mRNA expression. In vitro, galectin-7 regulated human placental villous RAS (AGT) and NADPH oxidase (CYBA, ICAM1 and VCAM1) mRNA expression. CONCLUSIONS: Overall, galectin-7 likely drives hypertension in preeclampsia via its direct regulation of multiple pathways associated with preeclampsia in the placenta. Galectin-7 may therefore be a therapeutic target to improve placental function and prevent preeclampsia.

Type de document: Article
Mots-clés libres: Galectin-7; Placenta; Preeclampsia; Reactive oxygen species; Renin-angiotensin system.
Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 29 déc. 2023 16:16
Dernière modification: 29 déc. 2023 16:16
URI: https://espace.inrs.ca/id/eprint/13425

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