1. Academic Validation
  2. Endothelial indoleamine 2,3-dioxygenase-1 regulates the placental vascular tone and is deficient in intrauterine growth restriction and pre-eclampsia

Endothelial indoleamine 2,3-dioxygenase-1 regulates the placental vascular tone and is deficient in intrauterine growth restriction and pre-eclampsia

  • Sci Rep. 2018 Apr 3;8(1):5488. doi: 10.1038/s41598-018-23896-0.
Pablo Zardoya-Laguardia 1 Astrid Blaschitz 1 Birgit Hirschmugl 2 Ingrid Lang 1 Sereina A Herzog 3 Liudmila Nikitina 1 Martin Gauster 1 Martin Häusler 2 Mila Cervar-Zivkovic 2 Eva Karpf 4 Ghassan J Maghzal 5 6 Chris P Stanley 5 Roland Stocker 5 6 Christian Wadsack 2 Saša Frank 7 Peter Sedlmayr 8
Affiliations

Affiliations

  • 1 Gottfried Schatz Research Centre for Cell Signalling, Metabolism and Ageing, Department of Cell Biology, Histology and Embryology, Medical University of Graz, Graz, 8010, Austria.
  • 2 Medical University of Graz, Department of Obstetrics and Gynaecology, Graz, 8036, Austria.
  • 3 Medical University of Graz, Institute for Medical Informatics, Statistics and Documentation, Graz, 8036, Austria.
  • 4 Medical University of Graz, Institute of Pathology, Graz, 8036, Austria.
  • 5 Victor Chang Cardiac Research Institute, Darlinghurst, NSW 2010, Australia.
  • 6 St Vincent's Clinical School, UNSW Medicine, Sydney, NSW 2052, Australia.
  • 7 Gottfried Schatz Research Centre for Cell Signalling, Metabolism and Ageing, Department of Molecular Biology and Biochemistry, Medical University of Graz, Graz, 8010, Austria.
  • 8 Gottfried Schatz Research Centre for Cell Signalling, Metabolism and Ageing, Department of Cell Biology, Histology and Embryology, Medical University of Graz, Graz, 8010, Austria. [email protected].
Abstract

Indoleamine 2,3-dioxygenase-1 (IDO1) mediates the degradation of L-tryptophan (L-Trp) and is constitutively expressed in the chorionic vascular endothelium of the human placenta with highest levels in the microvasculature. Given that endothelial expression of IDO1 has been shown to regulate vascular tone and blood pressure in mice under the condition of systemic inflammation, we asked whether IDO1 is also involved in the regulation of placental blood flow and if yes, whether this function is potentially impaired in intrauterine growth restriction (IUGR) and pre-eclampsia (PE). In the large arteries of the chorionic plate L-Trp induced relaxation only after upregulation of IDO1 using interferon gamma and tumor necrosis factor alpha. However, ex vivo placental perfusion of pre-constricted cotyledonic vasculature with L-Trp decreases the vessel back pressure without prior IDO1 induction. Further to this finding, IDO1 protein expression and activity is reduced in IUGR and PE when compared to gestational age-matched control tissue. These data suggest that L-Trp catabolism plays a role in the regulation of placental vascular tone, a finding which is potentially linked to placental and fetal growth. In this context our data suggest that IDO1 deficiency is related to the pathogenesis of IUGR and PE.

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