Oral Presentation Australasian Extracellular Vesicles Conference 2020

Placental Extracellular Nano-Vesicles From Preeclamptic Placentae Modify Maternal Vascular Resistance (#5)

Sandy Lau 1 , Carolyn Barrett 1 , Katie Groom 1 , Qi Chen 1 , Larry Chamley 1
  1. University of Auckland, Auckland, New Zealand

The human placenta is bathed in direct contact with maternal blood where nutrients transfer and waste removal occurs. Once thought as a waste product, the human placenta releases a large variety of extracellular vesicles into the adjacent maternal blood, which is then carried away and circulated throughout the body. Recent research has shown that these vesicles are not just cellular waste, but plays vital roles in the adaptation of maternal physiology which are critical for a successful pregnancy such as immune modulation and modulating vascular tone. In disorders of pregnancy, such as preeclampsia, the amount of extracellular vesicles released from the placenta increases but the cargo of these vesicles also changes. Placental extracellular vesicles from preeclamptic pregnancies have also been shown to activate endothelial cells in vitro. Given this, we hypothesised that placental extracellular vesicles from preeclamptic pregnancies are able to directly alter resistance of resistance arteries in pregnancy.

Placental extracellular nano-vesicles were isolated from human normal term or preeclamptic term placental explant culture by differential ultracentrifugation (200xg, 20,000xg, 100,000xg). Isolated vesicles were suspended in PBS and injected into pregnant mice, allowed to circulate for 30min, following which the mice were euthanised and the intestinal mesentery collected. Second order mesenteric vessels were isolated and mounted onto a wire myograph. The contractile and relaxation responses to vasodilatory (acetylcholine, sodium nitroprusside) and vasoconstrictive (phenylephrine, angiotensin II, endothelin-1) agents were tested.

Mesenteric arteries exposed to extracellular vesicles from a preeclamptic placenta exhibited a higher sensitivity to the vasoconstrictor angiotensin II and a lower sensitivity to the vasodilator sodium nitroprusside compared to extracellular vesicles from a normal pregnancy. These results suggest that the vascular modulation effects of placental extracellular nano-vesicles in preeclampsia are impaired towards a pro-constrictory phenotype and lowered sensitivity towards the nitric oxide donor sodium nitroprusside.