456 The involvement of placental and extracellular vesicles micro-RNA in the pathophysiology of gestational vascular complications

Abstract

Gestational vascular complications (GVC) include gestational hypertension and preeclampsia are leading cause of maternal morbidity and mortality. Extracellular vesicles (EV) are small, membrane-bound vesicles, budding from different cells and released to body fluids, containing various particles as microRNA (figure 1). Elevated levels of EV in GVC have been linked with vascular injury. MicroRNAs (miRNAs), are involved in various disorders, including GVC. We studied the role of placental and circulating EVs-miRNA in GVC and the effect of HP EVs versus GVC EVs on endothelial and trophoblast cells. Blood samples obtained from healthy non-pregnant (NP), healthy pregnant (HP) and GVC women. Plasma EVs' size and concentration were measured by Nanoparticles Tracking Analysis (NTA) and miRNA-EVs were screened. The effects of study cohort EVs on miRNA expression of early-stage trophoblasts and endothelial cells culture were evaluated. From 800 miRNAs screened, 104 significantly expressed in pregnant women, with higher concentrations contained in EVs. Alterations in expression of three miRNAs (miR-16-5p, miR-210 and miR-29b-3p), involved in gene regulations related to PI3K-Akt signaling pathway were detected. Expression of miR-16, miR-185 and miR-210 were low in EVs obtained from NP, elevated in HP-EVs and significantly decreased in GVC. Except for miR-29, which was upregulated in GVC, no changes were found in the levels of the other miRNAs in placenta sections of HP or GVC (figure 2). Additionally, exposure of villous trophoblasts to GVC-EVs significantly increased miR-29 in the treated cells, compared to HP-EVs but did not affects endothelial cells. miRNAs in EVs, play significant role in pathogenesis of GVC, with miR-16 and miR-210 are maternal factors, whereas miR-29 placental. This may distinguish between placental versus maternal pathology related to preeclampsia.View Large Image Figure ViewerDownload Hi-res image Download (PPT)