Pathogenesis of Preeclampsia |
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| Air date: | Wednesday, April 08, 2009, 3:00:00 PM |
| Category: | Wednesday Afternoon Lectures |
| Description: | Imbalance of angiogenic growth factors in the maternal circulation contributes to the pathogenesis of preeclampsia. Soluble fms-like tyrosine kinase 1 (sFlt1), an endogenous anti-angiogenic protein that antagonizes vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) appears to be a central player in this paradigm. Exogenous gene transfer of sFlt1 into pregnant rats using an adenoviral vector produced hypertension, proteinuria and glomerular endotheliosis, the classical pathological renal lesion of preeclampsia.
High serum sFlt1 and low serum free PlGF and free VEGF have been observed in preeclampsia. Abnormalities in these circulating angiogenic proteins are not only present during clinical preeclampsia, but also antedate clinical symptoms by several weeks. Another potential soluble factor secreted by the placenta that appears to be elevated in women with preeclampsia is soluble endoglin (sEng). Endoglin (Eng) is an angiogenic receptor expressed mainly on the surface of endothelial cells, but also placental syncytiotrophoblasts. Eng acts as a co-receptor for transforming growth factor-? (TGF-?, a potent pro-angiogenic molecule) signaling in endothelial cells. Eng mRNA is up-regulated in the preeclamptic placenta. In addition, the extra-cellular region of endoglin is proteolytically cleaved and that sEng is released in excess quantities into the circulation of preeclamptic patients. Furthermore, sEng appeared to exacerbate the vascular damage mediated by sFlt1 in pregnant rats resulting in severe preeclampsia-like illness including the development of HELLP syndrome and fetal growth restriction. What remains unknown is the etiology of the increased sFlt1 and sEng in preeclamptic patients and whether these markers can be used for the diagnosis and prediction of preeclampsia. Methods aimed at interfering sFlt1 and sEng may be a novel therapeutic strategy in patients with severe premature preeclampsia. The NIH Director's Wednesday Afternoon Lecture Series includes weekly scientific talks by some of the top researchers in the biomedical sciences worldwide. |
| Author: | S. Ananth Karumanchi |
| Runtime: | 75 minutes |
| Download: | Download
Video How to download a Videocast |
| CIT File ID: | 15026 |
| CIT Live ID: | 7622 |
| Permanent link: | http://videocast.nih.gov/launch.asp?15026 |
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Enhanced Audio Podcast | 1:08:06 |
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Enhanced Video Podcast | 1:08:06 | |