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Deciphering disease mechanisms underlying hypertensive pregnancy


   Institute of Cardiovascular and Medical Sciences

  Dr Delyth Graham, Dr Martin McBride  Applications accepted all year round  Self-Funded PhD Students Only

About the Project

Project outline:

The incidence of cardiovascular disease amongst women of child-bearing age is increasing. Consequently there is a greater prevalence of hypertensive disorders in pregnancy, in particular pre-eclampsia (PE), which is a leading cause of maternal and foetal morbidity and mortality. Despite its increased prevalence, the mechanisms underlying key pathological features of the disease remain unclear, and there are currently no effective clinical interventions. The stroke prone spontaneously hypertensive rat (SHRSP) is an established model of human cardiovascular disease, which exhibits chronic hypertension during pregnancy1. This model can be progressed to the more severe pregnancy complication, superimposed PE, through angiotensin II administration mid-gestation2. Our recent studies in this model have identified pregnancy- and disease- dependent alterations in the uterine artery transcriptome relative to the normotensive control strain3. In this project, the specific molecules and pathways identified in our previous SHRSP studies will be explored mechanistically to determine their role in the pathogenesis of hypertensive pregnancy in order to identify new targets of therapeutic or diagnostic interest.

Techniques used:

The student will receive training in a wide range of techniques, including animal models of hypertension and PE, cell culture, imaging, molecular biology approaches as well as RNASeq and other ‘Omics’ datsets and bioinformatic and pathway analysis. This PhD project will provide opportunities to develop an almost unique combination of in vivo, in vitro and molecular skills set.

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References

1. Small HY, Morgan H, Beattie E, Griffin S, Indahl M, Delles C, Graham D. Abnormal uterine artery remodelling in the stroke prone spontaneously hypertensive rat. Placenta. 2016 Jan;37:34-44.
2. Morgan HL, Butler E, Ritchie S, Herse F, Dechend R, Beattie E, McBride MW, Graham D. Modeling Superimposed Preeclampsia Using Ang II (Angiotensin II) Infusion in Pregnant Stroke-Prone Spontaneously Hypertensive Rats. Hypertension. 2018 Jul;72(1):208-218.
3. Scott K, Morgan HL, Delles C, Fisher S, Graham D, McBride MW. Distinct uterine artery gene expression profiles during early gestation in the stroke-prone spontaneously hypertensive rat. Physiological Genomics, 15 Mar 2021, 53(4):160-17
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