Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Weber, H.
The protein cargo differences of fetoplacental endothelial cell-derived exosomes of women with and without preeclampsia
Humanmedizin; [ Diplomarbeit ] Medizinische Universität Graz; 2023. pp. 246
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- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Hirschmugl Birgit
- Wadsack Christian
- Altmetrics:
- Abstract:
- Background: Preeclampsia is a severe pregnancy-associated syndrome whose pathomechanisms remain unclear. Since extracellular vesicles, in particular exosomes, are known for their impact on cell-to-cell communication, the question arises whether these vesicles may play key roles in the course of preeclampsia (PE). There is already evidence on the materno-placental side, but little is known about the fetoplacental compartment. We hypothesized differences in the fetoplacental vascular-derived exosomal sorting proteins between normal and PE placentas. Material and methods: This study analyzed extracellular vesicles from different fetoplacental vascular endothelial cells (n = 21). We isolated and compared endothelial cell-derived exosomes from fetoplacental arteries (n = 7, n = 3) and veins (n = 7, n = 4) from the chorionic plate of normal and PE placentas. All cells were grown under standard conditions. Exosomes were isolated per ultracentrifugation and analyzed regarding the quantity of their surface proteins – specifically ALIX, TSG101, syntenin-1, and CD81 – by immunoblotting. Additionally, we compared the exosomal size distribution and the total amount of protein per exosome, as a calculated variable, in both groups (vessel type and pregnancy course). Statistical analyses were performed in SPSS with Man-Whitney-U tests and a CI of 95%. Results: The expression of exosomal surface proteins derived from placental veins, compared to those derived from arteries, was similar. Most endosomal trafficking proteins were not expressed in a significantly different manner between PE and normal exosomes namely ALIX (p = 0.172), TSG101 (p = 0.128), and CD81 (p = 0.400). However, syntenin-1 as the most abundant trafficking protein showed decreased expression (p = 0.031) in PE exosomes. Size distribution and protein level per exosome did not differ significantly in all groups. Conclusion: Only syntenin-1, an adaptor protein and mediator for the endosomal sorting complex required for transport (ESCRT), showed a significant decrease in PE vesicles. As this protein affect the cytoskeletal-membrane organization, cell adhesion, protein trafficking and the activation of transcription factors and cell growth, it may contribute to the insufficiency of the placenta in PE. Further research is required to prove this hypothesis and figure out its exact role in the context of this syndrome.