(964) Preeclampsia leads to placental mediated dysregulation of Amphiregulin in macrophages

Preeclampsia is a leading cause of maternal morbidity and prematurity, characterized by maternal hypertension and proteinuria. The etiology is undefined yet, macrophages have been implicated in its pathogenesis. AREG encodes for the protein Amphiregulin which is member of the epidermal growth factor family and is highly expressed in the PAMM1a placental macrophage subset. Additionally, serum amphiregulin levels are reduced in preeclampsia. This project aims to differentiate expression levels of AREG in modeled placental macrophages.

Study Design:

Patients with preeclampsia were matched to controls within 2 weeks of gestational age. Placental tissue was collected from unlabored cesarean sections. Chorionic villi were dissected and used to generate placental conditioned media as previously described, fixed in 4% paraformaldehyde, or used for RNA purification. Placental conditioned media was incubated with THP-1 macrophages for 24 hours to generate placental conditioned macrophages. These are compared to polarized M1 (IFNγ, LPS) and M2 (IL4) controls.

Results:

We found that chorionic villi secrete high amounts of amphiregulin. The secretion varies by gestational age but is not statistically significantly different. Amphiregulin secretion by preeclampsia chorionic villi was not different than controls. Immunofluorescence reveals that amphiregulin localizes to probable CD14+ cells on the syncytium surface. In macrophages, AREG is secreted with exposure to placental conditioned media. Areg induction in placental conditioned macrophages is significantly reduced with preeclampsia. EGF family members HBEGF, VEGF, and EREG showed no difference in regulation as well as immunomodulatory factors IL10 and SOCS3 with preeclampsia versus controls.

Conclusion:

Our data suggests that macrophage regulation of amphiregulin is distinctly altered in preeclampsia and may be selective to the maternal derived, syncytiotrophoblast-associated PAMM1a macrophage subset. Future studies looking at the pathogenesis of this dysregulation may provide insight into markers for preeclampsia and the mechanisms underlying its pathogenesis.