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

作者：Nancy E. Freitag, Irene Tirado‐González, Gabriela Barrientos, Florian Herse, Victor L. Thijssen, Susanne M. Weedon-Fekjær, Herbert Schulz, Gerd Wallukat, Burghard F. Klapp, Tania Nevers, Surendra Sharma, Anne Cathrine Staff, Ralf Dechend, Sandra M. Blois · 发表于：Proceedings of the National Academy of Sciences · 年份：2013 · DOI：10.1073/pnas.1303707110 · 被引用次数：124 · 研究领域：Pregnancy and preeclampsia studies、Reproductive System and Pregnancy、Galectins and Cancer Biology

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.