Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Del Gaudio, I; Sreckovic, I; Zardoya-Laguardia, P; Bernhart, E; Christoffersen, C; Frank, S; Marsche, G; Illanes, SE; Wadsack, C.
Circulating cord blood HDL-S1P complex preserves the integrity of the feto-placental vasculature.
Biochim Biophys Acta Mol Cell Biol Lipids. 2020; 1865(4):158632-158632
Doi: 10.1016/j.bbalip.2020.158632
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- Führende Autor*innen der Med Uni Graz
- Del Gaudio Ilaria
- Wadsack Christian
- Co-Autor*innen der Med Uni Graz
- Bernhart Eva Maria
- Frank Sasa
- Marsche Gunther
- Sreckovic Ivana
- Zardoya Laguardia Pablo
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- 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. Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.
- Find related publications in this database (Keywords)
- Human placenta
- Pregnancy
- Bioactive lipids
- Placental vascular endothelium
- High-density lipoprotein