TY - JOUR
T1 - Circulating cord blood HDL-S1P complex preserves the integrity of the feto-placental vasculature
AU - Del Gaudio, Ilaria
AU - Sreckovic, Ivana
AU - Zardoya-Laguardia, Pablo
AU - Bernhart, Eva
AU - Christoffersen, Christina
AU - Frank, Saša
AU - Marsche, Gunther
AU - Illanes, Sebastian E.
AU - Wadsack, Christian
N1 - Funding Information:
The authors thank Susanne Kopp for excellent technical support. I. Del Gaudio, I. Sreckovic and P. Zardoya-Laguardia received funding from the Medical University of Graz within the PhD Program Molecular Medicine.
Publisher Copyright:
© 2020 The Author(s)
PY - 2020/4
Y1 - 2020/4
N2 - Perinatal and long-term offspring morbidities are strongly dependent on the preservation of placental vascular homeostasis during pregnancy. In adults, the HDL-apoM-S1P complex protects the endothelium and maintains vascular integrity. However, the metabolism and biology of cord blood-derived HDLs (referred to as neonatal HDL, nHDL) strikingly differ from those in adults. Here, we investigate the role of neonatal HDLs in the regulation of placental vascular function. We show that nHDL is a major carrier of sphingosine-1-phosphate (S1P), which is anchored to the particle through apoM (rs = 0.90, p < 0.0001) in the fetal circulation. Furthermore, this complex interacts with S1P receptors on the feto-placental endothelium and activates specifically extracellular signal-regulated protein kinases 1 and 2 (ERK) and phospholipase C (PLC) downstream signaling, promotes endothelial cell proliferation and calcium flux. Notably, the nHDL-S1P complex triggers actin filaments reorganization, leading to an enhancement of placental endothelial barrier function. Additionally, nHDL induces vasorelaxation of isolated placental chorionic arteries. Taken together, these results suggest that circulating nHDL exerts vasoprotective effects on the feto-placental endothelial barrier mainly via S1P signaling.
AB - Perinatal and long-term offspring morbidities are strongly dependent on the preservation of placental vascular homeostasis during pregnancy. In adults, the HDL-apoM-S1P complex protects the endothelium and maintains vascular integrity. However, the metabolism and biology of cord blood-derived HDLs (referred to as neonatal HDL, nHDL) strikingly differ from those in adults. Here, we investigate the role of neonatal HDLs in the regulation of placental vascular function. We show that nHDL is a major carrier of sphingosine-1-phosphate (S1P), which is anchored to the particle through apoM (rs = 0.90, p < 0.0001) in the fetal circulation. Furthermore, this complex interacts with S1P receptors on the feto-placental endothelium and activates specifically extracellular signal-regulated protein kinases 1 and 2 (ERK) and phospholipase C (PLC) downstream signaling, promotes endothelial cell proliferation and calcium flux. Notably, the nHDL-S1P complex triggers actin filaments reorganization, leading to an enhancement of placental endothelial barrier function. Additionally, nHDL induces vasorelaxation of isolated placental chorionic arteries. Taken together, these results suggest that circulating nHDL exerts vasoprotective effects on the feto-placental endothelial barrier mainly via S1P signaling.
KW - Bioactive lipids
KW - High-density lipoprotein
KW - Human placenta
KW - Placental vascular endothelium
KW - Pregnancy
KW - Lípidos bioactivos
KW - Lipoproteína de alta densidad
KW - Placenta humana
KW - Endotelio vascular placentario
KW - El embarazo
UR - http://www.scopus.com/inward/record.url?scp=85078071213&partnerID=8YFLogxK
U2 - 10.1016/j.bbalip.2020.158632
DO - 10.1016/j.bbalip.2020.158632
M3 - Article
C2 - 31954174
AN - SCOPUS:85078071213
SN - 1388-1981
VL - 1865
JO - Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
JF - Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
IS - 4
M1 - 158632
ER -