Negative Regulation of Soluble Flt-1 and Soluble Endoglin Release by Heme Oxygenase-1
Melissa J. Cudmore,Shakil Ahmad,Bahjat Al-Ani,Takeshi Fujisawa,Heather Coxall,Kunal Chudasama,Luke Devey,Stephen J. Wigmore,Allyah Abbas,Peter W. Hewett,Asif Ahmed +10 more
TLDR
It is demonstrated that the HO-1/CO pathway inhibits sFlt-1 and sEng release, providing compelling evidence for a protective role ofHO-1 in pregnancy, and identifies HO- 1 as a novel target for the treatment of preeclampsia.Abstract:
Preeclampsia is characterized clinically by hypertension and proteinuria. Soluble Flt-1 (sFlt-1; also known as soluble vascular endothelial growth factor receptor-1 [VEGFR-1]) and soluble endoglin (sEng) are elevated in preeclampsia, and their administration to pregnant rats elicits preeclampsia-like symptoms. Heme oxygenase-1 (HO-1) and its metabolite carbon monoxide (CO) exert protective effects against oxidative stimuli. Thus, we hypothesized that HO-1 upregulation may offer protection against preeclampsia by inhibiting sFlt-1 and sEng release.read more
Citations
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Preeclampsia, a Disease of the Maternal Endothelium The Role of Antiangiogenic Factors and Implications for Later Cardiovascular Disease
TL;DR: Preeclampsia is a systemic vascular disorder that may also affect the liver and the brain in the mothers and is named not only for the liver involvement, but also for the disorder of the coagulation system that develops.
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Preeclampsia: Pathophysiology, Challenges, and Perspectives
Sarosh Rana,Elizabeth R. Lemoine,Elizabeth R. Lemoine,Joey P. Granger,S. Ananth Karumanchi,S. Ananth Karumanchi +5 more
TL;DR: The current evidence for the role of abnormal placentation and therole of placental factors such as the antiangiogenic factor, sFLT1 (soluble fms-like tyrosine kinase 1) in the pathogenesis of the maternal syndrome of preeclampsia is discussed.
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Extracellular control of TGFβ signalling in vascular development and disease
ten Dijke P,Helen M. Arthur +1 more
TL;DR: It seems that elastic extracellular matrix (ECM) components have a crucial role in controlling TGFβ signalling, while soluble and membrane bound forms of TGF β co-receptors add further layers of regulation.
Journal ArticleDOI
Pathogenesis of Preeclampsia
TL;DR: The recent discoveries of upregulated antiangiogenic factors provide promise for future testing to predict and diagnose preeclampsia as well as therapeutic targets for amelioration of the clinical disease.
Journal ArticleDOI
Pre-eclampsia: pathogenesis, novel diagnostics and therapies.
Elizabeth A. Phipps,Elizabeth A. Phipps,Ravi Thadhani,Ravi Thadhani,Thomas Benzing,S. Ananth Karumanchi,S. Ananth Karumanchi +6 more
TL;DR: The pathogenic role of antiangiogenic proteins released by the placenta in the development of pre-eclampsia is discussed and novel therapeutic strategies directed at restoring the angiogenic imbalance observed during pre- eClampsia are reviewed.
References
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Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia
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TL;DR: It is confirmed that placental soluble fms-like tyrosine kinase 1 (sFlt1), an antagonist of VEGF and placental growth factor (PlGF), is upregulated in preeclampsia, leading to increased systemic levels of sFlt 1 that fall after delivery, and observations suggest that excess circulating sFelt1 contributes to the pathogenesis of preeClampsia.
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Richard J. Levine,Sharon Maynard,Cong Qian,Kee-Hak Lim,Lucinda England,Kai F. Yu,Enrique F. Schisterman,Ravi Thadhani,Benjamin P. Sachs,Franklin H. Epstein,Bahaeddine M Sibai,Vikas P. Sukhatme,S. Ananth Karumanchi +12 more
TL;DR: Alterations in the levels of sFlt-1 and free PlGF were greater in women with an earlier onset of preeclampsia and in women in whom preeClampsia was associated with a small-for-gestational-age infant.
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