Preeclampsia, a hypertensive disease of human pregnancy, may present early or late onset depending on whether symptoms appear before or after 34 weeks gestation. These variants of preeclampsia may have different pathogenic mechanisms. After a preeclamptic pregnancy, women are at increased risk of early cardiovascular disease (CVD) mortality. We hypothesized that placental EVs are a mechanistic link between preeclampsia and CVD.
Small, large and macro EVs isolated from normotensive, early or late onset preeclamptic placentae, by differential centrifugation, were injected into spontaneously hypertensive rats (n=19). Blood pressure was monitored by tail cuff and cardiovascular function by echocardiography for 12 months. Vascular function was assessed by wire myography.
Systolic blood pressure was significantly increased in the animals receiving early onset preeclamptic EVs (<0.015), compared to the normotensive EVs, from 3 months post-injection. Whereas, the difference in systolic blood pressure for the late onset preeclamptic EVs was significantly (p<0.017) increased only to nine months post-injection. Body weight, heart rate and stroke volume were not significantly affected by the preeclamptic EVs but wire myography indicated that resistance vessels demonstrated significantly enhanced responsiveness to vasoconstrictors after treatment with preeclamptic EVs.
Our data show that administration of human placental EVs was well-tolerated by the animals. However, both early- and late-onset preeclamptic placental EVs caused long-term changes in cardiovascular function with sustained increases in blood pressure which might be explained in part by the heightened responsiveness of resistance blood vessels to vasoconstrictors. Placental EVs may be an important mechanistic link between preeclampsia and later CVD.