Abstract 030: Low Indoleamine 2,3 Dioxygenase Activity in Pregnancy are Associated With Increased Carotid-Femoral Pulse Wave Velocity in Preeclampsia

Abstract

Preeclampsia is a prevalent multi-organ complication of pregnancy that is characterized by gestational hypertension and proteinuria. Immunologic and vascular alterations clearly occur before clinical disease. One mechanism that could explain both the exaggerated immune response and vascular dysfunction involves indoleamine 2, 3 dioxygenase (IDO). We have previously shown that the IDO-KO mouse replicates the vascular and obstetric phenotypes of human preeclampsia. We hypothesize that decreases in IDO activity are associated with vascular dysfunction as measured by carotid-femoral pulse wave velocity (PWV), a measure of aortic stiffness. We test this hypothesis in this nested case control study of two similarly recruited prospective cohorts (Preeclampsia IDO Vascular Function and Perinatal Outcomes study IRB: 201009701), and the (Early Vascular Dysfunction and Elevated Copeptin in Human Preeclampsia study IRB: 201503789). A total of 136 control and 13 preeclamptic pregnant women were recruited to measure vascular function and immunovascular factors throughout gestation. Plasma IDO activity was colorimetrically measured and trimester specific quartiles for IDO activity were calculated. PWV was measured via tonometry. Highest and lowest IDO activity quartile groups were compared. First trimester IDO activity was not associated with differences in PWV throughout gestation. Lower second and third trimester IDO activity was associated with higher PWV throughout gestation (1 st trimester: 6.8 ± 0.3 vs 5.5 ± 0.2, P<0.001; 2 nd trimester: 7.1 ± 0.4 vs 5.1 ± 0.2 P<0.001; 3 rd trimester 6.5 ± 0.2 vs 5.9 ± 0.2 m/s, P<0.001). Even after controlling for preeclampsia, third trimester IDO activity was inversely associated with PWV (Beta IDO=-11, p=0.023 and Beta preeclampsia=0.150, p=0.753). Consistent with our hypothesis, our data demonstrate IDO activity is inversely associated with vascular dysfunction. Future studies will elucidate the molecular immunovascular mechanisms underlying this association in preeclampsia.