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

PY - 2020

Y1 - 2020

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

U2 - 10.1016/j.bbalip.2020.158632

DO - 10.1016/j.bbalip.2020.158632

M3 - Journal article

C2 - 31954174

AN - SCOPUS:85078071213

VL - 1865

JO - B B A - Molecular and Cell Biology of Lipids

JF - B B A - Molecular and Cell Biology of Lipids

SN - 1388-1981

IS - 4

M1 - 158632

ER -