Syncytiotrophoblast extracellular vesicles significantly reduced angiotensin II responsiveness in uterine arteries from wildtype pregnant mice, but this adaptation was absent in LOX-1 overexpressing mice.
Do STBEVs alter angiotensin II responsiveness via LOX-1 and AT1 receptors in mouse uterine arteries during pregnancy?
STBEVs reduce angiotensin II responsiveness in normal pregnancy via LOX-1, suggesting a role in normal adaptations to pregnancy, while oxidized LDL increases vasoconstriction, potentially contributing to preeclampsia.
p-value: p=<0.05
Vascular complications in pregnancy (e.g. preeclampsia) are a major source of maternal and foetal morbidity and mortality, and may be due to excessive release of placental syncytiotrophoblast-derived extracellular vesicles (STBEVs) into the maternal circulation. Increased activity of the multi-ligand scavenger receptor Lectin-like Oxidized LDL Receptor-1 (LOX-1) is associated with vascular dysfunction, and LOX-1 has been shown to interact with angiotensin II receptor type 1 (AT1). We hypothesized that STBEVs contribute to vascular dysfunction via LOX-1 and AT1 receptors during pregnancy. Uterine arteries from late pregnant wildtype and LOX-1 overexpressing mice were incubated overnight with or without STBEVs and vascular function was assessed using wire myography. STBEV-incubation decreased angiotensin II responsiveness only in wildtype mice, which coincided with decreased AT1 contribution and expression. Thus, STBEVs reduced angiotensin II responsiveness in normal pregnancy, but not in conditions of increased LOX-1 expression, suggesting that STBEVs (via LOX-1) play a role in normal adaptations to pregnancy. Oxidized LDL (a LOX-1 ligand) increased angiotensin II-induced vasoconstriction in STBEV-incubated arteries from both mouse strains, suggesting that the LOX-1 pathway may be involved in complicated pregnancies with elevated STBEVs and oxidized LDL levels (such as preeclampsia). These data increase our understanding of vascular complications during pregnancy.
Spaans et al. (Wed,) conducted a other in Pregnancy-induced vascular adaptations. Syncytiotrophoblast extracellular vesicles (STBEVs) vs. Vehicle (physiological salt solution) was evaluated on Angiotensin II-induced vasoconstriction (p=<0.05). Syncytiotrophoblast extracellular vesicles significantly reduced angiotensin II responsiveness in uterine arteries from wildtype pregnant mice, but this adaptation was absent in LOX-1 overexpressing mice.
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