Oral Presentation ESA-SRB-APEG-NZSE 2022

Placental extracellular vesicles: a novel link of preeclampsia to future cardiovascular disease   (#46)

Yourong Feng 1 , Sandy Lau 1 , Katie Groom 2 , Qi Chen 1 , Carolyn Barrett 3 , Larry Chamley 1
  1. Department of Obstetrics And Gynecology , the University of Auckland, Auckland, New Zealand
  2. Liggins Institute, the University of Auckland, Auckland, New Zealand
  3. Department of Physiology, the University of Auckland, Auckland, New Zealand

Cardiovascular disease (CVD) is the leading cause of death in women1 and the risk increases significantly following preeclampsia (PE), a hypertensive disorder of pregnancy. Extracellular vesicles (EVs) are lipid bilayer-enclosed structures that are extruded from cells to control the function of remote cells/organs. During pregnancy, the placenta extrudes vast numbers of EVs into the maternal circulation and there is increasing evidence that EVs trigger preeclampsia2. We hypothesized that preeclamptic placental EVs cause increased CVD risk following preeclampsia.
EVs were isolated from late-onset preeclampsia (LOPE), early-onset preeclampsia (EOPE), or normotensive placentae and administered to female spontaneously hypertensive rats (SHR) via tail veins. Systolic blood pressure (SBP) was recorded by tail-cuff. The vasoreactivity of SHRs mesenteric arteries was measured using a wire myograph. The artery remodeling was determined by histological analysis.
SBP in the LOPE group was significantly increased, with an average of 43.58 mmHg 12-month post-EVs injection. In the EOPE group, there was a larger increase in SBP after 12 months (63.37±12.25 mmHg). In contrast, SBP in the normotensive group showed a significantly smaller increase, with an average of 31.99±4.72 mmHg 12 months after exposure to placental EVs. Wire myography revealed a significant increase in vasoconstriction in response to phenylephrine and U46619 in vessels exposed to LOPE placental EVs. Vessels exposed to EOPE EVs also showed increased vasoconstriction to U46619 and endothelin-1 compared to the normotensive group. Additionally, the relaxation response of mesenteric arteries from the EOPE group was significantly decreased in response to ACh. Small artery thickening was markedly increased in LOPE and EOPE groups.
Our data support the concept that placental EVs have long-lasting effects on the maternal cardiovascular system and altered SBP is associated with abnormal vascular reactivity induced by placental EVs. Preeclamptic EVs may be a mechanistic link between preeclampsia and later CVD.

  1. 1. Cardiovascular diseases (CVDs). 2021; Available from: https://www.who.int/en/news-room/fact-sheets/detail/cardiovascular-diseases-(cvds). 2. Shen F, Wei J, Snowise S, DeSousa J, Stone P, Viall C, Chen Q and Chamley LW. Trophoblast debris extruded from preeclamptic placentae activates endothelial cells: a mechanism by which the placenta communicates with the maternal endothelium. Placenta. 2014;35(10):839-47.