The levels of angiogenic and anti-angiogenic molecule concentrations in pregnancy based disorders in the maternal and fetal circulation

Afzal, Islam (2013). The levels of angiogenic and anti-angiogenic molecule concentrations in pregnancy based disorders in the maternal and fetal circulation. University of Birmingham. M.Phil.

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OBJECTIVE: To determine if preeclampsia (PE) and intrauterine growth restriction (IUGR) is associated with differing levels of angiogenic and anti-angiogenic growth factors in both maternal and fetal circulation and the effect of heme oxygenase-1 (HO-1) and honokiol, an AKT phosphorylation inhibitor, on endothelial cells (EC) on these anti-angiogenic growth factors.

DESIGN: 1st test ; Nested case-controlled plasma samples from 165 pregnant patients assayed for soluble vascular endothelial growth factor 1 (sVEGFR-1) soluble endoglin (sEng), vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) in Spain during 2001-2007. 2nd test; knockdown of HO-1 on EC and assayed to observe the effects on sVEGFR-1 levels released. 3rd test; 24 hour treatment to honokiol, an extract from the magnolia tree, on endothelial cells to observe the effect on sVEGFR-1 and sEng release.

RESULTS: In the PE specimens, maternal sVEGFR-1 levels increased more than 3-fold compared with gestational controls, fetals levels remained unchanged. The levels of sEng, and PlGF did not significantly change and the levels of VEGF 8-fold more than the controls. Free sVEGFR-1 was found to be in 4-fold excess in the PE state compared to the gestational control. siRNA of HO-1 was found to cause an elevation in VEGF activated sVEGFR-1 release. Honokiol was found to decrease VEGF activated sVEGFR-1 release with increasing concentration and increase sEng release in the presence of various growth factors.

CONCLUSION: There is an excess of sVEGFR-1 present in PE. Heme oxygenase 1 mediates sVEGFR-1 release and honokiol decreases sVEGFR-1 release from EC.

Type of Work: Thesis (Masters by Research > M.Phil.)
Award Type: Masters by Research > M.Phil.
College/Faculty: Colleges (2008 onwards) > College of Medical & Dental Sciences
School or Department: School of Clinical and Experimental Medicine, Academic Department of Obstetrics and Gynacology
Funders: None/not applicable
Subjects: R Medicine > RG Gynecology and obstetrics


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