The placenta, oxidative stress and the maternal inflammatory response in pre-eclampsia. (360G-Wellcome-079862_Z_06_Z)
This program develops our long-standing research into the pathophysiology of the specific pregnancy disorder, pre-eclampsia. We have proposed that the maternal syndrome arises from a dysfunctional systemic inflammatory response, involving the entire inflammatory network, including endothelium. There are three stages: the response of the specific placental cell, trophoblast, and its mitochondria to the oxidative stress that is a fundamental problem in pre-eclampsia; release into the maternal circulation of trophoblast-derived microparticles and other factors, which signal to maternal endothelium and circulating inflammatory cells; and the triggering of maternal inflammatory responses. We will investigate mechanisms involved in all stages, relating to:i) the importance of lipid rafts and caveolin-1 to syncytiotrophoblast mitochondrial integrity and resistance to oxidative stress; ii) the contribution of apoptosis and necrosis to syncytiotrophoblast microparticle release, both physiological and pathological; iii) the importance of microparticle shedding as a signal to maternal endothelial and immune cells and iv) the potential role of NKT cells in determining the systemic inflammatory responses to processed microparticulate syncytiotrophoblast antigens in normal and pre-eclamptic pregnancies. We seek a more complete understanding of the placental causes of complexities of end-stage pre-eclampsia. The ultimate aim is to facilitate the development of scientifically targeted therapies.
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Grant Details
Amount Awarded | 1110722 |
Applicant Surname | Sargent |
Approval Committee | Physiological Sciences Funding Committee |
Award Date | 2006-05-03T00:00:00+00:00 |
Financial Year | 2005/06 |
Grant Programme: Title | Programme Grant |
Internal ID | 079862/Z/06/Z |
Lead Applicant | Prof Ian Sargent |
Other Applicant(s) | Dr Elizabeth Linton, Prof Christopher Redman |
Partnership Value | 1110722 |
Planned Dates: End Date | 2011-12-31T00:00:00+00:00 |
Planned Dates: Start Date | 2006-07-01T00:00:00+00:00 |
Recipient Org: Country | United Kingdom |
Region | South East |