Abstract P323: Arginine Vasopressin and Indoleamine 2,3 Dioxygenase: The Early Immunovascular Interface in Preeclampsia

Abstract

Preeclampsia (PreE), a hypertensive disease of pregnancy, causes maternal and fetal health complications. Abnormal placental development/angiogenesis and poor immunoregulation (involving T cells, Indoleamine 2, 3 Dioxygenase (IDO), and dendritic cells) are central to the development of PreE. IDO, produced by regulatory immune cells, degrades tryptophan to arrest inflammatory T cell proliferation and induces T regulatory cell development. Our data and others show decreased IDO placental expression from human preeclamptic pregnancies. We published that deletion of IDO (IDO KO) in pregnant mice results in pathognomonic glomerular endotheliosis, proteinuria, and intrauterine growth restriction, hallmark features of PreE. Our group also demonstrated that, plasma copeptin, a stable bio-marker of vasopressin (AVP) secretion, is elevated early in human PreE pregnancies; and AVP infusion into wild-type C57BL/6J dams phenocopies human PreE, including increased inflammatory T cells and highly activated dendritic cells. Here, we test our hypothesis that AVP (via copeptin measurement) is elevated in the IDO KO mouse model of PreE and that IDO activity is decreased in the AVP mouse model of PreE. Copeptin, measured by ELISA, was elevated in both the placenta (2.4±0.2 vs. 1.7±0.2 pg/mg, p=0.03) and maternal serum (2.1±0.2 vs. 1.2±0.4 pg/mg, p=0.03) from IDO KO pregnancies compared to wild-type at gestational day (GD) 18. In our chronic infusion of AVP model of PreE (24 ng/hour), GD 18 colorimetric IDO activity was decreased by 22% in the maternal kidney (N=10 per group) and by 27% in the amniotic fluid (saline N=8 vs. AVP N=12) of AVP-infused dams in comparison to controls. Collectively, these data demonstrate an inverse relationship between IDO activity and copeptin expression in PreE pregnancies. As both IDO and AVP sit at the crossroads between vascular and immune dysfunction, these data suggest that the IDO-AVP interaction may contribute to the maternal and fetal renal phenotype observed in preeclampsia.