Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/35391
Full metadata record
DC FieldValueLanguage
dc.contributor.authorHo, Yih-Hsuan-
dc.contributor.authorHarper, Alesia-
dc.contributor.authorDu Plessis, Inge-
dc.contributor.authorAtukorala, Ishara-
dc.contributor.authorKadife, Elif-
dc.date.accessioned2024-07-21T23:08:09Z-
dc.date.available2024-07-21T23:08:09Z-
dc.date.issued2024-07-
dc.identifier.urihttps://ahro.austin.org.au/austinjspui/handle/1/35391-
dc.descriptionResearchFest 2024en_US
dc.description.abstractThe therapeutic potential of YAP activation for Fetal Growth Restriction Background Therapeutic treatments for Fetal Growth Restriction (FGR) are urgently needed. A primary cause of FGR are placental insufficiencies, often due to poorly developed placental vasculature. We propose a novel therapeutic approach by targeting the Yes Associated Protein (YAP), a growth factor involved in angiogenesis that is downregulated in FGR placentas. This study aims to investigate the therapeutic potential of YAP activation in improving Human Umbilical Vein Endothelial Cell growth (HUVEC), function and blood vessel development in placental tissues. Methods Human placental explants and HUVECs (n=5/condition) were obtained from normotensive term pregnancies. These were treated with YAP-activating compounds XMU (0.5-5µM), TRULI (0.5-5µM) and TDI (0.001-0.5µM). We confirmed YAP activation and investigated its molecular effects through gene (qPCRs) and protein (Western Blots) analysis. We assessed functional effects of YAP using colorimetric proliferation (0-72hrs) and staining of CD31 (endothelial marker) positive cells in tissues. Results HUVECs exhibited varying levels of response to the compounds, showing a high degree of patient dependency. TRULI reduces the inactive form of YAP by 42% after 48 hours of treatment, while XMU and TDI show a decrease of 20% and 25% respectively. At 72 hours after treatment, the compounds cause an approximate 20% increase in cell proliferation at the lower doses, compared to vehicle-treated cells. Furthermore, molecular analysis showed that Connective Tissue Growth Factor (CTGF), a downstream target of YAP, was upregulated two-fold on average. These are validated in placental explants treated with the compounds for 24 hours, where there is increased CD31 endothelial cell marker detection. Conclusion We demonstrate that restoring YAP activity can lead to small but potentially biologically significant increases in proliferation and function. Importantly, our chosen compounds do not appear to deregulate cell growth or death and demonstrates the ability to reverse YAP dysregulation to increase blood vessel endothelial cell proliferation and support angiogenesis.en_US
dc.subjectFetal Growth Restrictionen_US
dc.subjectPlacental Insufficiencyen_US
dc.titleYAP activation may restore placental blood vessel supply as a therapy for Fetal Growth Restrictionen_US
dc.typeConference Presentationen_US
dc.identifier.affiliationM1. Obstetrics Diagnostics and Therapeutics Group, University of Melbourne, Heidelberg, Vic., Australia; 2. Department of Obstetrics, Gynaecology and Newborn Health, University of Melbourne, Mercy Hospital for Women, Heidelberg, Vic., Australia; 3. Lisa Hui Group, University of Melbourne, Heidelberg, Vic., Australia;en_US
dc.description.conferencenameResearchFest 2024en_US
dc.description.conferencelocationAustin Healthen_US
dc.type.contentTexten_US
dc.type.contentImageen_US
item.openairetypeConference Presentation-
item.cerifentitytypePublications-
item.grantfulltextopen-
item.fulltextWith Fulltext-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
Appears in Collections:ResearchFest abstracts
Files in This Item:
File Description SizeFormat 
FINAL austin posterr.pdfHo et al., ResearchFest 2024297.75 kBAdobe PDFThumbnail
View/Open
Show simple item record

Page view(s)

78
checked on Nov 26, 2024

Download(s)

24
checked on Nov 26, 2024

Google ScholarTM

Check


Items in AHRO are protected by copyright, with all rights reserved, unless otherwise indicated.