1. Angiogenic factors in preeclampsia
Sharon E Maynard, M.D.
Assistant Professor
Departments of Medicine,
Biochemistry & Mol Biology,
and Obstetrics and Gynecology
(202)

2. 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

3. 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.

4. 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 GWU
Assess efficacy as screening test in high-risk populations
Eventually use as a biomarker to target innovative therapies

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