W/F Orange Final Research Project
Overview and Background
Preeclampsia is a medical condition in pregnant women, often characterized by hypertension (high blood pressure) and proteinuria (high amounts of protein in the urine). This condition affects about 10% of pregnancies. Research has found that high levels of a specific angiogenic factor produced by the placenta, tyrosine kinase 1 (sFlt1), have been observed during and prior to clinical manifestation of preeclampsia.
Research Problem and Goals
We would like to induce preeclampsia in pregnant mice, and then, using siRNA gene regulation, target sFlt1 for down regulation. After knocking down sFlt1 in preeclamptic mice, we will then compare the blood pressures and urine protein concentrations of the knock down preeclamptic mice with those of normal preeclamptic mice to understand the relationship between the angiogenic factor sFlt1 and preeclamptic pregnancies.
Details and Methods
Zhou et al. have discovered that preeclampsia can be induced in mice by introducing angiotensin receptor agonistic autoantibodies. Using this method, we would induce preeclampsia in pregnant mice. Then, using siRNA knockdown, we would knock down sFlt1 in one group of the preeclamptic mice and compare their blood pressures and urine protein concentrations with the preeclamptic mice that have not had sFlt1 knocked down.
Because a correlation has been found between preeclampsia and high serum concentrations of sFlt1, we are interested in investigating if there is a causal relationship as well. We hypothesize that by knocking down sFlt1, we will see a decrease in blood pressure and protein concentration in urine in the preeclamptic mice treated with siRNA. We are also interested in investigating the
- Zhou, Cissy C, Yujin Zhang, Roxanna A Irani, Hong Zhang, Tiejuan Mi1, Edwina J Popek, M John Hicks, Susan M Ramin, Rodney E Kellems, 'and' Yang Xia. "Angiotensin receptor agonistic autoantibodies induce pre-eclampsia in pregnant mice." Nature Medicine 1427 July 2008 855-862. Web.5 May 2009.
- Reddy A, Suri S, Sargent IL, Redman CWG, Muttukrishna S (2009) Maternal Circulating Levels of Activin A, Inhibin A, sFlt-1 and Endoglin at Parturition in Normal Pregnancy and Pre-Eclampsia. PLoS ONE 4(2):e4453. Epub 2009 Feb 11.
- Tjoa ML, Levine RJ, Karumanchi SA. "Angiogenic factors and preeclampsia." Front Biosci. Jan 2007 12:2395-402.
- Walter P. Muttera and S. Ananth Karumanchi. "Molecular mechanisms of preeclampsia." Microvascular Research 75 January 2008 1:1-8.
- Lam C, Lim KH, Karumanchi SA. "Circulating angiogenic factors in the pathogenesis and prediction of preeclampsia." Hypertension. 2005 Nov;46(5):1077-85. Epub 2005 Oct 17.