Interfering with Gal-1–mediated angiogenesis contributes to the pathogenesis of preeclampsia

• Published in: Proceedings of the National Academy of Sciences - PNAS 2013-07, Vol.110 (28), p.11451-11456
• Main Authors: Freitag, Nancy, Tirado-González, Irene, Barrientos, Gabriela, Herse, Florian, Thijssen, Victor L. J. L., Weedon-Fekjær, Susanne M., Schulz, Herbert, Wallukat, Gerd, Klapp, Burghard F., Nevers, Tania, Sharma, Surendra, Staff, Anne Cathrine, Dechend, Ralf, Blois, Sandra M.
• Format: Article
• Language: English
• Subjects: Angiogenesis; Animals; Binding sites; Biological Sciences; Dams; Disease Models, Animal; Endothelial cells; Female; Fetal growth retardation; Fetus; Galectin 1 - metabolism; Galectin 1 - physiology; Humans; Mice; Neovascularization, Physiologic - physiology; Pathogenesis; Placenta; Placenta - metabolism; Placentation; Pre-Eclampsia - etiology; Pre-Eclampsia - physiopathology; Preeclampsia; Pregnancy; Proteins; Receptors; Rodents; Signal transduction; Trophoblasts - cytology
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1303707110

Preeclampsia (PE) is a pregnancy-specific disorder characterized by sudden onset of hypertension and proteinuria in the second half of pregnancy (>20 wk). PE is strongly associated with abnormal placentation and an excessive maternal inflammatory response. Galectin-1 (Gal-1), a member of a family of carbohydrate-binding proteins, has been shown to modulate several processes associated with placentation and to promote maternal tolerance toward fetal antigens. Here, we show that Gal-1 exhibits proangiogenic functions during early stages of pregnancy, promoting decidual vascular expansion through VEGF receptor 2 signaling. Blocking Gal-1–mediated angiogenesis or lectin, galactoside-binding, soluble, 1 deficiency results in a spontaneous PE-like syndrome in mice, mainly by deregulating processes associated with good placentation and maternal spiral artery remodeling. Consistent with these findings, we observed a down-regulation of Gal-1 in patients suffering from early onset PE. Collectively, these results strengthen the notion that Gal-1 is required for healthy gestation and highlight Gal-1 as a valuable biomarker for early PE diagnosis.