Intralipid Infusion in Pregnant Rats Induces Plasma Angiogenic Imbalance, Inflammation, and Intrauterine Growth Restriction

Abstract

Preeclampsia is a pregnancy specific disorder characterized by maternal hypertension and proteinuria and is associated with low birth weight, vascular dysfunction, and an increase in inflammatory and anti‐angiogenic factors. Recent studies have shown that obese women are 4 times more likely to develop preeclampsia. In addition, preeclamptic patients have higher levels of circulating free fatty acids (FFA) and other lipids compared to normal pregnant women. While a high fat diet can lead to reduced uteroplacental perfusion, vascular and placental dysfunction, the mechanism whereby lipids contribute to these outcomes in preeclampsia is unknown. To test the hypothesis that lipid administration induces placental and vascular dysfunction, pregnant rats were infused intravenously with 20% Intralipids (50–100 μL/kg/min) over a 2 h period on gestational days (GD) 11–18 or ‐19. On GD 19, mean arterial pressure (MAP), pup weight, placental weight, blood and tissues were collected. Third order mesentery arteries and aortas were used for vascular reactivity studies, and placental villi were cultured for 48 h to measure the production of angiogenic factors ex vivo. Infusion of intralipids resulted in no change in MAP, vascular reactivity, or placental villous angiogenic factors. However, infusion of intralipids in pregnant rats caused a significant increase in placental weight (0.66 ± 0.01 g vs 0.61 ± 0.01 g; p<0.01) and fetal absorption (13.8 ± 5.9% vs 0.85 ± 0.85%; p<0.05), and a decrease in pup weight (2.37 ± 0.02 g vs 2.57 ± 0.02 g; p<0.01) compared to control rats. Furthermore, plasma tumor necrosis factor‐alpha (TNF‐α; 24.82 ± 6.21 pg/mL vs 12.24 ± 1.52 pg/mL; p<0.05) and soluble fms‐like tyrosine kinase (sFLT‐1; 20.08 ± 5.76 pg/mL vs 4.42 ± 2.04 pg/mL; p<0.05) were increased, while plasma placental growth factor (PlGF; 28.57 ± 5.65 pg/mL vs 51.19 ± 8.82 pg/mL; p<0.05) was decreased in intralipid‐infused pregnant rats compared to control rats. These data indicate that increasing lipid intake during pregnancy induces intrauterine growth restriction coupled with a pro‐inflammatory and anti‐angiogenic state. Further studies to determine the factors associated with intralipid‐induced fetal outcomes are warranted and could provide a better understanding of the role of elevated lipids/FFA as a risk factor for preeclampsia.Support or Funding InformationP01HL051971, P20GM104357, and T32HL105324.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.