TY - JOUR
T1 - Interfering with Gal-1-mediated angiogenesis contributes to the pathogenesis of preeclampsia
AU - Freitag, Nancy
AU - Tirado-Gonzaĺez, Irene
AU - Barrientos, Gabriela
AU - Herse, Florian
AU - Thijssen, Victor L.J.L.
AU - Weedon-Fekjær, Susanne M.
AU - Schulz, Herbert
AU - Wallukat, Gerd
AU - Klapp, Burghard F.
AU - Nevers, Tania
AU - Sharma, Surendra
AU - Staff, Anne Cathrine
AU - Dechend, Ralf
AU - Blois, Sandra M.
PY - 2013/7/9
Y1 - 2013/7/9
N2 - 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.
AB - 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.
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U2 - 10.1073/pnas.1303707110
DO - 10.1073/pnas.1303707110
M3 - Article
C2 - 23798433
AN - SCOPUS:84879973172
SN - 0027-8424
VL - 110
SP - 11451
EP - 11456
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 28
ER -