Show simple item record

dc.contributor.authorDutta, Suchismita
dc.contributor.authorLai, Andrew
dc.contributor.authorScholz-Romero, Katherin
dc.contributor.authorShiddiky, Muhammad JA
dc.contributor.authorYamauchi, Yusuke
dc.contributor.authorMishra, Jay S
dc.contributor.authorRice, Gregory E
dc.contributor.authorHyett, Jon
dc.contributor.authorKumar, Sathish
dc.contributor.authorSalomon, Carlos
dc.description.abstractSmall extracellular vesicles (sEVs) released from the extravillous trophoblast (EVT) are known to regulate uterine spiral artery remodeling during early pregnancy. The bioactivity and release of these sEVs differ under differing oxygen tensions and in aberrant pregnancy conditions. Whether the placental cell-derived sEVs released from the hypoxic placenta contribute to the pathophysiology of preeclampsia is not known. We hypothesize that, in response to low oxygen tension, the EVT packages a specific set of proteins in sEVs and that these released sEVs interact with endothelial cells to induce inflammation and increase maternal systemic blood pressure. Using a quantitative MS/MS approach, we identified 507 differentially abundant proteins within sEVs isolated from HTR-8/SVneo cells (a commonly used EVT model) cultured at 1% (hypoxia) compared with 8% (normoxia) oxygen. Among these differentially abundant proteins, 206 were up-regulated and 301 were down-regulated (P < 0.05), and they were mainly implicated in inflammation-related pathways. In vitro incubation of hypoxic sEVs with endothelial cells, significantly increased (P < 0.05) the release of GM-CSF, IL-6, IL-8, and VEGF, when compared with control (i.e. cells without sEVs) and normoxic sEVs. In vivo injection of hypoxic sEVs into pregnant rats significantly increased (P < 0.05) mean arterial pressure with increases in systolic and diastolic blood pressures. We propose that oxygen tension regulates the release and bioactivity of sEVs from EVT and that these sEVs regulate inflammation and maternal systemic blood pressure. This novel oxygen-responsive, sEVs signaling pathway, therefore, may contribute to the physiopathology of preeclampsia.
dc.publisherPortland Press Ltd.
dc.relation.ispartofjournalClinical Science
dc.subject.fieldofresearchBiomedical and clinical sciences
dc.subject.keywordsScience & Technology
dc.subject.keywordsLife Sciences & Biomedicine
dc.subject.keywordsMedicine, Research & Experimental
dc.subject.keywordsResearch & Experimental Medicine
dc.titleHypoxia-induced small extracellular vesicle proteins regulate proinflammatory cytokines and systemic blood pressure in pregnant rats
dc.typeJournal article
dc.type.descriptionC1 - Articles
dcterms.bibliographicCitationDutta, S; Lai, A; Scholz-Romero, K; Shiddiky, MJA; Yamauchi, Y; Mishra, JS; Rice, GE; Hyett, J; Kumar, S; Salomon, C, Hypoxia-induced small extracellular vesicle proteins regulate proinflammatory cytokines and systemic blood pressure in pregnant rats, Clinical Science, 2020, 134 (6), pp. 593-607
gro.hasfulltextNo Full Text
gro.griffith.authorShiddiky, Muhammad J.

Files in this item


There are no files associated with this item.

This item appears in the following Collection(s)

  • Journal articles
    Contains articles published by Griffith authors in scholarly journals.

Show simple item record