45. Effects of syncytiotrophoblast extracellular vesicles (STBEVs) on endothelium-dependent vasodilation in uterine arteries from lectin-like oxidized ldl receptor-1 (LOX-1) overexpressing mice during pregnancy

Abstract

Introduction Placental factors, such as syncytiotrophoblast extracellular vesicles (STBEVs), have been suggested to contribute to maternal endothelial vascular dysfunction in women with preeclampsia (PE). The lectin-like oxidized LDL receptor-1 (LOX-1) is a multi-ligand scavenger receptor; and in women with PE both STBEV levels and LOX-1 expression are elevated. We used heterozygous LOX-1 overexpressing (LOX-1OE) mice to further investigate the role of LOX-1 and STBEVs in vascular dysfunction during pregnancy. Hypothesis We hypothesized that STBEVs activate LOX-1 and contribute to vascular dysfunction in mouse uterine arteries of LOX-1OE mice, but not in WT controls. Methods Uterine arteries were obtained from late pregnant (gestational day 18; term = day 19) LOX-1OE mice (carrying a bovine LOX-1 transgene) and WT controls (−/−). Isolated vessels were incubated overnight in the absence (n = 8) or presence of STBEVs (200 μg/ml, n = 5–7) from control pregnant women. Using wire myography, endothelium-dependent vasodilation responses to methylcholine (MCh) were assessed with or without L-NAME (pan nitric oxide synthase inhibitor), superoxide dismutase (SOD) or oxidized LDL (oxLDL). Results Endothelium-dependent vasodilation to MCh was unchanged following STBEV-incubation in both mouse strains. In WT mice, nitric oxide did not contribute to vasodilation, while there was a nitric oxide contribution to vasodilation in STBEV-incubated arteries (p Discussion Interestingly, both LOX-1OE and STBEV-exposure increased nitric oxide contribution to relaxation; perhaps as a compensatory mechanism. OxLDL (a potential contributing factor in women with PE and dyslipidemia) impaired endothelial-dependent relaxation in the presence of increased LOX-1 expression during pregnancy. These data suggest that increased LOX-1 expression in women with PE could contribute to impaired vascular function.