Sphingolipid Signature of Human Feto-Placental Vasculature in Preeclampsia.
Arteries
/ metabolism
Ceramides
/ metabolism
Chorion
/ metabolism
Endothelial Cells
/ metabolism
Endothelium, Vascular
/ metabolism
Female
Fetus
/ metabolism
Gene Expression
/ physiology
Humans
Lysophospholipids
/ metabolism
Maternal-Fetal Exchange
/ physiology
Placenta
/ metabolism
Placental Circulation
/ physiology
Pre-Eclampsia
/ metabolism
Pregnancy
Signal Transduction
/ physiology
Sphingolipids
/ metabolism
Sphingomyelins
/ metabolism
Sphingosine
/ analogs & derivatives
bioactive lipids
feto-placental endothelium
human placenta
placental vasculature
preeclampsia
sphingolipid metabolism
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
04 Feb 2020
04 Feb 2020
Historique:
received:
16
12
2019
revised:
29
01
2020
accepted:
03
02
2020
entrez:
9
2
2020
pubmed:
9
2
2020
medline:
18
11
2020
Statut:
epublish
Résumé
Bioactive sphingolipids are emerging as key regulators of vascular function and homeostasis. While most of the clinical studies have been devoted to profile circulating sphingolipids in maternal plasma, little is known about the role of the sphingolipid at the feto-placental vasculature, which is in direct contact with the offspring circulation. Our study aims to compare the sphingolipid profile of normal with preeclamptic (PE) placental chorionic arteries and isolated endothelial cells, with the goal of unveiling potential underlying pathomechanisms in the vasculature. Dihydrosphingosine and sphingomyelin (SM) concentrations (C16:0-, C18:0-, and C24:0- sphingomyelin) were significantly increased in chorionic arteries of preeclamptic placentas, whereas total ceramide, although showing a downward trend, were not statistically different. Moreover, RNA and immunofluorescence analysis showed impaired sphingosine-1-phosphate (S1P) synthesis and signaling in PE vessels. Our data reveal that the exposure to a deranged maternal intrauterine environment during PE alters the sphingolipid signature and gene expression on the fetal side of the placental vasculature. This pathological remodeling consists in increased serine palmitoyltransferase (SPT) activity and SM accrual in PE chorionic arteries, with concomitance impairment endothelial S1P signaling in the endothelium of these vessels. The increase of endothelial S1P phosphatase, lyase and S1PR2, and blunted S1PR1 expression support the onset of the pathological phenotype in chorionic arteries.
Identifiants
pubmed: 32033121
pii: ijms21031019
doi: 10.3390/ijms21031019
pmc: PMC7037072
pii:
doi:
Substances chimiques
Ceramides
0
Lysophospholipids
0
Sphingolipids
0
Sphingomyelins
0
sphingosine 1-phosphate
26993-30-6
Sphingosine
NGZ37HRE42
safingol
OWA98U788S
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Déclaration de conflit d'intérêts
The authors declare no conflict of interest
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