Abstract P3046: Elevated Free Fatty Acids During Pregnancy Promote Vascular Impairment, Uteroplacental Dysfunction And Angiogenic Imbalance In Rats

Abstract

Preeclampsia (PE) is a pregnancy-specific syndrome affecting 5-8% of pregnancies and is associated with vascular dysfunction and an increase in anti-angiogenic factors. Recent studies have shown that obese women are 4 times more likely to develop preeclampsia, and obesity/preeclampsia has been shown to increase circulating free fatty acids (FA). However, the role of FA on preeclamptic characteristics, such as uteroplacental and vascular dysfunction, as well as angiogenic imbalance has yet to be determined. To test the hypothesis that FAs induce a placental ischemic-like phenotype, pregnant rats were infused daily (IV) from gestational days (GD) 13-18 with specific free FA: 10mM Oleate and Palmitate, 4mM Linoleic Acid, and 0.8mM Arachadonic Acid. On GD 19, MAP, blood and tissues were collected. Third order mesentery arteries and aortas were used for vascular reactivity studies. Placental villi from normal pregnant rats exposed to FA ex vivo were examined for production of angiogenic factors. While infusion of FA resulted in no change in MAP, pup or placental weight, there was a trend for an increase in fetal reabsorption (9.7±3.3% vs 2.4±1.3%; p=0.07) and decrease in plasma PlGF in FA-infused rats (506±22vs 583±35 pg/mL; p=0.07), indicating moderate impairment in uteroplacental function in FA-infused pregnant rats compared to vehicle normal pregnant rats. Aortas of FA-infused pregnant rats revealed impaired Phe-induced vasoconstriction beginning at 3E -6.5 M of Phe (31.3±7.5 vs 70.8±11.4; p=<0.02), while vasorelaxation was attenuated in mesenteric arteries of FA-infused pregnant rats compared to normal pregnant rats (p<0.01). Moreover, FA caused an increase in sFlt-1 (533±34 vs 181±7 pg/mL; p<0.01) and sFlt-1:PlGF ratio (4.8±.1 vs 3.2±.2; p<0.01) in placental explants compared to vehicle. These data suggest that elevated FA during pregnancy, at levels comparable to those observed in preeclampsia, promote uteroplacental dysfunction, angiogenic imbalance, and impaired vascular reactivity in rats. Further studies to examine the mechanisms associated with FA-induced uteroplacental outcomes in pregnancy could elucidate the role of elevated FA as a risk factor for placental ischemia.