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Publications in Scientific Journals:

R. Atallah, J. Gindlhuber, W. Platzer, E. Tatzl, R. Birner-Grünberger, C Wadsack, P. Luschnig, W. Toller, J. Strutz, S. Rittchen, A. Heinemann:
"SUCNR1 Is Expressed in Human Placenta and Mediates Angiogenesis: Significance in Gestational Diabetes";
International Journal of Molecular Sciences, 22 (2021), 12048; 1 - 19.



English abstract:
Placental hypervascularization has been reported in pregnancy-related pathologies such as
gestational diabetes mellitus (GDM). Nevertheless, the underlying causes behind this abnormality
are not well understood. In this study, we addressed the expression of SUCNR1 (cognate succinate
receptor) in human placental endothelial cells and hypothesized that the succinate-SUCNR1 axis
might play a role in the placental hypervascularization reported in GDM. We measured significantly
higher succinate levels in placental tissue lysates from women with GDM relative to matched controls.
In parallel, SUCNR1 protein expression was upregulated in GDM tissue lysates as well as in isolated
diabetic fetoplacental arterial endothelial cells (FpECAds). A positive correlation of SUCNR1 and
vascular endothelial growth factor (VEGF) protein levels in tissue lysates indicated a potential
link between the succinate-SUCNR1 axis and placental angiogenesis. In our in vitro experiments,
succinate prompted hallmarks of angiogenesis in human umbilical vein endothelial cells (HUVECs)
such as proliferation, migration and spheroid sprouting. These results were further validated in
fetoplacental arterial endothelial cells (FpECAs), where succinate induced endothelial tube formation.
VEGF gene expression was increased in response to succinate in both HUVECs and FpECAs. Yet,
knockdown of SUCNR1 in HUVECs led to suppression of VEGF gene expression and abrogated the
migratory ability and wound healing in response to succinate. In conclusion, our data underline
SUCNR1 as a promising metabolic target in human placenta and as a potential driver of enhanced
placental angiogenesis in GDM.

Keywords:
succinate; SUCNR1; GDM; placenta; endothelial cells; angiogenesis


"Official" electronic version of the publication (accessed through its Digital Object Identifier - DOI)
http://dx.doi.org/10.3390/ijms222112048

Electronic version of the publication:
https://publik.tuwien.ac.at/files/publik_301074.pdf


Created from the Publication Database of the Vienna University of Technology.