Angiogenic factors in preeclampsia

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Presentation transcript:

Angiogenic factors in preeclampsia Sharon E Maynard, M.D. Assistant Professor Departments of Medicine, Biochemistry & Mol Biology, and Obstetrics and Gynecology (202) 741-2283 smaynard@mfa.gwu.edu

The placenta – perhaps as as a result of ischemia – secretes a factor into the maternal circulation which produces systemic endothelial dysfunction Preeclampsia features Maternal serum produces endothelial dysfunction Placental ischemia; failure of normal placental vasculogenesis Gene expression profiling

Increased sFlt1 in preeclampsia sFlt1 is a soluble splice variant of the VEGF receptor Flt1 sFlt1 is secreted by placenta and antagonizes VEGF and PlGF in the circulation sFlt1 administered to pregnant rats results in a preeclampsia syndrome, including classical renal lesion (endotheliosis) Other evidence… Other evidence: sFlt1 mimics the effect of PE serum on endothelial cells when added to normal serum. Cancer patients treated with vegf antagonists get hypertension and proteinuria VEGF podocyte specific k-o mouse had similar renal lesion Smokers have lower risk PE. Nicotine is known to enhance endothelial VEGF expression and smokers have decreased levels of sFlt1. Provides the first cohesive explanation of why smoking might be protective.

Current and Future Projects Characterization of sFlt1 dysregulation in preeclampsia Other sFlt1 alternative splice variants -mRNA (qPCR), protein (LC, IP, PAGE, MS) Transcription control of flt1 expression in placenta: promoter regulatory elements sFlt1 for screening and prediction of preeclampsia Goal to establish high-risk pregnancy cohort @ GWU Assess efficacy as screening test in high-risk populations Eventually use as a biomarker to target innovative therapies

Colleagues and Collaborators Biochemistry: Tim McCaffrey Fatah Kashanchi Mohammad Heydarian Ob/Gyn: Charles Macri John Larsen Susie Bathgate