Journal ArticleDOI
Soluble endoglin contributes to the pathogenesis of preeclampsia.
Shivalingappa Venkatesha,Mourad Toporsian,Chun Lam,Jun-ichi Hanai,Tadanori Mammoto,Yeon Mee Kim,Yeon Mee Kim,Yuval Bdolah,Kee-Hak Lim,Hai Tao Yuan,Towia A. Libermann,Isaac E. Stillman,Drucilla J. Roberts,Patricia A. D'Amore,Franklin H. Epstein,Frank W. Sellke,Roberto Romero,Roberto Romero,Vikas P. Sukhatme,Michelle Letarte,S. Ananth Karumanchi +20 more
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TLDR
A novel placenta-derived soluble TGF-β coreceptor, endoglin (sEng), which is elevated in the sera of preeclamptic individuals, correlates with disease severity and falls after delivery, suggest that sEng may act in concert with sFlt1 to induce severe preeclampsia.Abstract:
Preeclampsia is a pregnancy-specific hypertensive syndrome that causes substantial maternal and fetal morbidity and mortality. Maternal endothelial dysfunction mediated by excess placenta-derived soluble VEGF receptor 1 (sVEGFR1 or sFlt1) is emerging as a prominent component in disease pathogenesis. We report a novel placenta-derived soluble TGF-beta coreceptor, endoglin (sEng), which is elevated in the sera of preeclamptic individuals, correlates with disease severity and falls after delivery. sEng inhibits formation of capillary tubes in vitro and induces vascular permeability and hypertension in vivo. Its effects in pregnant rats are amplified by coadministration of sFlt1, leading to severe preeclampsia including the HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome and restriction of fetal growth. sEng impairs binding of TGF-beta1 to its receptors and downstream signaling including effects on activation of eNOS and vasodilation, suggesting that sEng leads to dysregulated TGF-beta signaling in the vasculature. Our results suggest that sEng may act in concert with sFlt1 to induce severe preeclampsia.read more
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Journal ArticleDOI
Soluble endoglin and other circulating antiangiogenic factors in preeclampsia.
Richard J. Levine,Chun Lam,Cong Qian,Kai F. Yu,Sharon Maynard,Benjamin P. Sachs,Baha M. Sibai,Franklin H. Epstein,Roberto Romero,Roberto Romero,Ravi Thadhani,S. Ananth Karumanchi +11 more
TL;DR: Rising circulating levels of soluble endoglin and ratios of sFlt1:PlGF herald the onset of preeclampsia, which was greatest among women in the highest quartile of the control distributions for both biomarkers but not for either biomarker alone.
Journal ArticleDOI
Decidual NK cells regulate key developmental processes at the human fetal-maternal interface
Jacob H. Hanna,Debra Goldman-Wohl,Yaron Hamani,Inbal Avraham,Caryn Greenfield,Shira Natanson-Yaron,Diana Prus,Leonor Cohen-Daniel,Tal I. Arnon,Irit Manaster,Roi Gazit,Vladimir Yutkin,Daniel Benharroch,Angel Porgador,Eli Keshet,Simcha Yagel,Ofer Mandelboim +16 more
TL;DR: It is shown that dNK cells, but not peripheral blood–derived NK subsets, regulate trophoblast invasion both in vitro and in vivo by production of the interleukin-8 and interferon-inducible protein–10 chemokines.
Journal ArticleDOI
The "Great Obstetrical Syndromes" are associated with disorders of deep placentation.
TL;DR: Criteria for the classification of defective deep placentation into 3 types is proposed based on the degree of restriction of remodeling and the presence of obstructive lesions in the myometrial segment of the spiral arteries.
Journal ArticleDOI
Inflammatory Cytokines in Vascular Dysfunction and Vascular Disease
TL;DR: Genetic and pharmacological tools to decrease the production of cytokines or to diminish their effects using cytokine antagonists could provide new approaches in the management of inflammatory vascular disease.
Journal ArticleDOI
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.
References
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Journal ArticleDOI
Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia
Sharon Maynard,Jiang Yong Min,Jaime R. Merchan,Kee-Hak Lim,Jianyi Li,Susanta Mondal,Towia A. Libermann,James P. Morgan,Frank W. Sellke,Isaac E. Stillman,Franklin H. Epstein,Vikas P. Sukhatme,S. Ananth Karumanchi +12 more
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.
Journal ArticleDOI
Circulating Angiogenic Factors and the Risk of Preeclampsia
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.
Journal ArticleDOI
Latest advances in understanding preeclampsia.
TL;DR: Recent work on the causes of preeclampsia is summarized, which reveals a new mode of maternal immune recognition of the fetus, relevant to the condition, and circulating factors derived from the placenta are now better understood.
Journal ArticleDOI
Preeclampsia: an endothelial cell disorder.
James M. Roberts,Robert N. Taylor,Thomas J. Musci,George M. Rodgers,Carl A. Hubel,Margaret K. McLaughlin +5 more
TL;DR: It is proposed that poorly perfused placental tissue releases a factor(s) into the systemic circulation that injuries endothelial cells and set in motion a dysfunctional cascade of coagulation, vasoconstriction, and intravascular fluid redistribution that results in the clinical syndrome of preeclampsia.