Circulating cord blood HDL-S1P complex preserves the integrity of the feto-placental vasculature

Ilaria Del Gaudio; Ivana Sreckovic; Pablo Zardoya-Laguardia; Eva Bernhart; Christina Christoffersen; Saša Frank; Gunther Marsche; Sebastian E. Illanes; Christian Wadsack

doi:10.1016/j.bbalip.2020.158632

Circulating cord blood HDL-S1P complex preserves the integrity of the feto-placental vasculature

Ilaria Del Gaudio, Ivana Sreckovic, Pablo Zardoya-Laguardia, Eva Bernhart, Christina Christoffersen, Saša Frank, Gunther Marsche, Sebastian E. Illanes, Christian Wadsack^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

18 Scopus citations

Abstract

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 (r^s = 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.

Translated title of the contribution	El complejo HDL-S1P de sangre de cordón circulante preserva la integridad de la vasculatura fetoplacentaria
Original language	English
Article number	158632
Journal	Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Volume	1865
Issue number	4
DOIs	https://doi.org/10.1016/j.bbalip.2020.158632
State	Published - Apr 2020

Bibliographical note

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)

Keywords

Bioactive lipids
High-density lipoprotein
Human placenta
Placental vascular endothelium
Pregnancy

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10.1016/j.bbalip.2020.158632

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Del Gaudio, I., Sreckovic, I., Zardoya-Laguardia, P., Bernhart, E., Christoffersen, C., Frank, S., Marsche, G., Illanes, S. E., & Wadsack, C. (2020). Circulating cord blood HDL-S1P complex preserves the integrity of the feto-placental vasculature. Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids, 1865(4), Article 158632. https://doi.org/10.1016/j.bbalip.2020.158632

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title = "Circulating cord blood HDL-S1P complex preserves the integrity of the feto-placental vasculature",

abstract = "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.",

keywords = "Bioactive lipids, High-density lipoprotein, Human placenta, Placental vascular endothelium, Pregnancy, L{\'i}pidos bioactivos, Lipoprote{\'i}na de alta densidad, Placenta humana, Endotelio vascular placentario, El embarazo",

author = "{Del Gaudio}, Ilaria and Ivana Sreckovic and Pablo Zardoya-Laguardia and Eva Bernhart and Christina Christoffersen and Sa{\v s}a Frank and Gunther Marsche and Illanes, {Sebastian E.} and Christian Wadsack",

note = "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: {\textcopyright} 2020 The Author(s)",

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Del Gaudio, I, Sreckovic, I, Zardoya-Laguardia, P, Bernhart, E, Christoffersen, C, Frank, S, Marsche, G, Illanes, SE & Wadsack, C 2020, 'Circulating cord blood HDL-S1P complex preserves the integrity of the feto-placental vasculature', Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids, vol. 1865, no. 4, 158632. https://doi.org/10.1016/j.bbalip.2020.158632

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

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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 -

Circulating cord blood HDL-S1P complex preserves the integrity of the feto-placental vasculature

Abstract

Bibliographical note

Keywords

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