Galectin-7 dysregulates renin-angiotensin-aldosterone and NADPH oxide synthase pathways in preeclampsia
- Author(s)
- Menkhorst, E; Zhou, W; Santos, L; Zhang, JG; St-Pierre, Y; Young, MJ; Dimitriadis, E;
- Journal Title
- Pregnancy and Hypertension
- Abstract
- 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.
- Publisher
- Elsevier
- Keywords
- Galectin-7; Placenta; Preeclampsia; Reactive oxygen species; Renin-angiotensin system
- Research Division(s)
- Blood Cells And Blood Cancer
- PubMed ID
- 36183583
- Publisher's Version
- https://doi.org/10.1016/j.preghy.2022.09.008
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2022-10-05 02:14:44
Last Modified: 2022-10-05 02:17:05