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Open AccessCommunication

Neonatal HDL Counteracts Placental Vascular Inflammation via S1P–S1PR1 Axis

1
Department of Obstetrics and Gynecology, Medical University of Graz, 8036 Graz, Austria
2
Department of Biomedical Sciences, University of Copenhagen, 1165 Copenhagen, Denmark
3
Department of Clinical Biochemistry, Rigshospitalet, 2100 Copenhagen, Denmark
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(3), 789; https://doi.org/10.3390/ijms21030789
Received: 17 December 2019 / Revised: 20 January 2020 / Accepted: 21 January 2020 / Published: 25 January 2020
(This article belongs to the Special Issue Molecular Aspects of Inflammation in Pregnancy)
Placental inflammation and dysfunction during pregnancy are associated with short- and long-term adverse outcomes for the offspring. However, the mechanisms of vascular protection at the feto-placental interface are still poorly investigated. The high-density lipoprotein (HDL) associated sphingosine-1-phosphate (S1P) has been described as a powerful anti-inflammatory complex. This study aimed to elucidate the role of cord blood-derived HDL (nHDL) in feto-placental endothelial dysfunction. Here, we report that the exposure of primary fetal placental arterial endothelial cell (fPAEC) to healthy nHDL-S1P attenuated the ability of TNFα to activate NF-κB signaling and increase the expression of pro-inflammatory markers. Moreover, the angiotensin II (AngII)-induced reactive oxygen species (ROS) production was blunted in the presence of nHDL, whereas it was preserved when the cells were preincubated with S1P receptor antagonists, suggesting that S1P accounts for the vascular protective function of nHDL at the feto-placental unit. These results highlight the importance of HDL and S1P metabolism and signaling in pregnancy pathophysiology. View Full-Text
Keywords: neonatal high-density lipoprotein; vascular inflammation; feto-placental dysfunction; sphingosine-1-phosphate neonatal high-density lipoprotein; vascular inflammation; feto-placental dysfunction; sphingosine-1-phosphate
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Del Gaudio, I.; Hendrix, S.; Christoffersen, C.; Wadsack, C. Neonatal HDL Counteracts Placental Vascular Inflammation via S1P–S1PR1 Axis. Int. J. Mol. Sci. 2020, 21, 789.

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