Placental extracellular vesicles (pEVs) are known to cause endothelial cell activation in vitro1 and are heavily implicated in the development of preeclampsia2. Early-onset preeclampsia is associated with postpartum arterial stiffness, microvascular dysfunction and chronic hypertension; however, it is unknown whether pEVs are responsible for these lingering vascular changes. This study aimed to evaluate the effects of pEVs on maternal vascular function in spontaneously hypertensive rats (SHRs).
pEVs were isolated from cultured human term-placenta explants from either normotensive (n=7) or early-onset preeclamptic pregnancies (n=5). Each rat received 5 intravenous injections (315 μg protein each) of EVs obtained from one placenta, between days 8-18 of pregnancy. Two weeks postpartum, the function of second and third-order mesenteric arteries were evaluated using wire myography.
Resistance arteries from SHRs that received pEVs from early-onset preeclamptic pregnancies were more responsive to the vasoconstrictor U46619, a thromboxane A2 analogue, than vessels from the normotensive group (p<0.0001). There were no differences in vessel response to vasoconstrictors, phenylephrine or endothelin-1 (p=0.2735 and p=0.1590, respectively). Vessels from SHRs in the early-onset treatment group were less responsive to the vasodilator acetylcholine than the normotensive treatment group (p=0.0112). There was no difference in response to the vasodilator sodium nitroprusside (p=0.6215).
U46619 and acetylcholine both act on the vasculature in an endothelium-dependent manner. Whereas phenylephrine, endothelin-1 and sodium nitroprusside are endothelium-independent. These results suggest that preeclamptic pEVs interact with endothelial cells during pregnancy to produce lasting negative effects on the maternal vasculature. Ongoing effects of preeclamptic pEVs in early postpartum may be an indication of long-term changes to the maternal vasculature after a preeclamptic pregnancy. Further investigation will be required to establish whether EVs from preeclamptic placentae are, at least partly, responsible for the increased risk of vascular dysfunction and hypertension after pregnancy in women affected by early-onset preeclampsia.