(L-464) Human Umbilical Vein Endothelial Cells from Preeclamptic Pregnancies secrete more chemokines in a microphysiological system.

Introduction:: Preeclampsia (PE) is a disorder in pregnancy clinically diagnosed primarily by increased blood pressure. Human umbilical endothelial cells (HUVECs) isolated from PE pregnancies show dysfunction via increased endothelial monolayer permeability and decreased Ca2+ signaling. Increased inflammation and immune activation have been noted in blood and placenta from PE; and suspected to mediate endothelial dysfunction in PE. The intrinsic inflammatory profile of endothelial cells themselves in PE compared to normal pregnancy is not well understood and studied here.

Materials and Methods:: Methods – Passage 1 primary HUVECs were isolated from normal pregnant women or PE women. Cells from 6 normal and 6 preeclamptic patients were utilized in this study – with 3 males and 3 females in each of the groups. Microfluidic µvessels (μvessels) were generated via mold casting of a tubular structure within a collagen gel that was subsequently lined with 20,000 HUVECs/μvessel and maintained in culture for 3 days with no further treatment. We analyzed media from these μvessels for cytokine and chemokine secretion from HUVECs.

Results, Conclusions, and Discussions:: Results: PE HUVEC μvessels show at least a two-fold change in secretion of the following cytokines and chemokines: 2.24 in GM-CSF, 2.12 in GRO, 3.27 in IL-6. Additionally, t-test revealed significant changes in secretion of GRO, IL-6, IL-8, IP-10. PE male HUVEC μvessels show ≥2 fold changes in the following - 2.24 in GRO, 2.83 in IL-6, 2.01 in IP-10. PE female HUVEC μvessels show ≥2 fold changes in - GM-CSF – 2.64, Fractalkine -2, GRO - 2.03, IL-6 – 3.91.
Conclusion/Discussion: HUVEC μvessels are found to be proinflammatory in PE, mainly secreting increased GM-CSF, GRO, IL-6, IL-8, and IP-10. These results point to the ability of endothelial cells to secrete inflammatory or immune-recruiting proteins in preeclampsia. The increase in chemokine secretion in endothelial cells in the absence of the PE microenvironment through serum, plasma or immune cells is suggestive of a programmed inflammatory or immune-modulating property of HUVECs in PE warranting further studies. We propose to use this microphysiological system to elucidate the cross-talk between inflammation and endothelial function in PE.

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