Impaired clearance of placental extracellular vesicles after delivery could be a risk factor for developing endothelial dysfunction later in women with a history of preeclampsia

OBJECTIVES: Placental extracellular vesicles are released into maternal circulation during pregnancy and are rapidly cleared by maternal cells, including endothelial and immune cells. However, the clearance of placental extracellular vesicles in maternal circulation has not been fully investigated in both physiological and pathological conditions. miRNAs clustered on chromosome 19 (C19MC) are unique to primate human placentae and can be detected in placental extracellular vesicles. Here, we investigated the clearance of placental extracellular vesicles by measuring plasma levels of C19MC miRNAs. METHODS: We measured nine C19MC miRNAs (miR-526a-5p, miRNA-527, miRNA-1283, miRNA-498-5p, miRNA-520-3p, miRNA-519a-3p, miRNA-512-3p, miRNA-515-3p, and miRNA-516-3p) in maternal circulation three to five days before and three days after delivery in healthy pregnancies (n = 20) and preeclampsia (n = 10). The levels of these miRNAs were compared before and after delivery. RESULTS: In healthy pregnancies, levels of all nine C19MC miRNAs in maternal circulation significantly decreased, while only four C19MC miRNAs significantly decreased after delivery in preeclampsia, compared to predelivery levels. Additionally, compared to healthy pregnancies, the plasma levels of the five C19MC miRNAs were substantially higher, and the rest of the four C19MC miRNAs remained unchanged after delivery in preeclampsia. Furthermore, transfection with individual or combination mimics of C19MC miRNAs (miRNA-526a-5p, miRNA-515-3p, and miRNA-516-3p) into endothelial cells increased monocyte adhesion to endothelial cells. CONCLUSION: Our findings suggest impaired clearance of placental extracellular vesicles after delivery in maternal circulation in preeclampsia, and the impaired clearance may contribute to endothelial dysfunction and increase the risk of developing long-term cardiovascular diseases in women with a history of preeclampsia.