Presenter : Sarah Johnson
Mentor : Jeffrey Gilbert
Major : Biology/Human Physiology
Poster 28
The pregnancy-specific hypertension known as preeclampsia (PE) is widely observed worldwide and is recognized as a leading contributor to sickness and death of a mother and her baby. This pervasive condition is yet to be fully characterized, as is an effective therapy of symptom relief outside of inducing early delivery. We have recently reported treatment with an adenosine-mimetic, AICA-riboside (AICAR), in an experimental model of PE reduces the onset of PE-like characteristics; however, the underlying mechanisms are poorly understood. Therefore, our hypothesis was AICAR would initiate cytoprotective and pro-angiogenic stimulation in cultured placental tissue explants, and this effect would be mediated by the adenosine (ENT1/2) transporter. Tissues were cultured at 37°C for 12 hours in physiologic normoxic (8% O2) or hypoxic (1.5% O2) conditions, and treated with AICAR (2mM) and an adenosine transporter blocker (dipyridamole, DPM) (100μM). Explants treated with AICAR exhibited a decreased (P<0.05) secreted sFlt-1 in both O2 conditions, and DPM blocked this effect. The energy regulatory protein AMPKα phosphorylation was elevated in the tissues treated with AICAR, but was not statistically significant (0.1>P>0.05). Through modeling placental ischemia ex vivo, we have demonstrated AICAR decreas- es placental secretion of sFlt-1, mediated by adenosine transport activity. In concert with our previous in vivo studies with AICAR, this study further supports a placental specific mechanism of AICAR’s actions in vivo.