Effect on the Production of Soluble Endoglin from Human Choriocarcinoma Cells by Preeclampsia Sera

Aoki, Yoichi; Yamamoto, Tatsuo; Chishima, Fumihisa; Nakamura, Asuka; Asanuma, Aki; Suzuki, Manami

doi:10.1111/j.1600-0897.2011.01086.x

Cited by 12 publications

(10 citation statements)

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“…Human studies have also shown that levels of Hmox are decreased in patients with preeclampsia (21)(22)(23)(24)(25)(26)(27). Furthermore, the addition of sera from patients with preeclampsia led to decreased levels of Hmox in vitro (28). Conversely, increased gene expression of Hmox was shown to decrease circulating levels of sFlt-1 (29).…”

Section: Heme Oxygenase Pathwaymentioning

confidence: 97%

Preeclampsia: Updates in Pathogenesis, Definitions, and Guidelines

Phipps

Prasanna

Brima

et al. 2016

CJASN

462

328

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Preeclampsia is becoming an increasingly common diagnosis in the developed world and remains a high cause of maternal and fetal morbidity and mortality in the developing world. Delay in childbearing in the developed world feeds into the risk factors associated with preeclampsia, which include older maternal age, obesity, and/or vascular diseases. Inadequate prenatal care partially explains the persistent high prevalence in the developing world. In this review, we begin by presenting the most recent concepts in the pathogenesis of preeclampsia. Upstream triggers of the well described angiogenic pathways, such as the heme oxygenase and hydrogen sulfide pathways, as well as the roles of autoantibodies, misfolded proteins, nitric oxide, and oxidative stress will be described. We also detail updated definitions, classification schema, and treatment targets of hypertensive disorders of pregnancy put forth by obstetric and hypertensive societies throughout the world. The shift has been made to view preeclampsia as a systemic disease with widespread endothelial damage and the potential to affect future cardiovascular diseases rather than a selflimited occurrence. At the very least, we now know that preeclampsia does not end with delivery of the placenta. We conclude by summarizing the latest strategies for prevention and treatment of preeclampsia. A better understanding of this entity will help in the care of at-risk women before delivery and for decades after.

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Section: Heme Oxygenase Pathwaymentioning

confidence: 97%

Preeclampsia: Updates in Pathogenesis, Definitions, and Guidelines

Phipps

Prasanna

Brima

et al. 2016

CJASN

462

328

View full text Add to dashboard Cite

show abstract

“…27 Interestingly, sera from pregnant women with preeclampsia can upregulate the levels of endoglin mRNA and induce the release of sEng in choriocarcinoma cells. 28 Endoglin is a transmembrane auxiliary receptor for transforming growth factor-␤ that modulates cellular responses to multiple members of the transforming growth factor-␤ family. 29 Endoglin is highly expressed on proliferating endothelial cells and syncytiotrophoblasts, including the trophoblast cell line JAR, 29 -31 and regulates trophoblast differentiation along the invasive pathway in human placental villous explants.…”

Section: Clinical Perspective On P 2624mentioning

confidence: 99%

Oxysterol-Induced Soluble Endoglin Release and Its Involvement in Hypertension

et al. 2012

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Background-Ischemia in the placenta is considered the base of the pathogenesis of preeclampsia, a pregnancy-specific syndrome in which soluble endoglin (sEng) is a prognostic marker and plays a pathogenic role. Here, we investigated the effects of hypoxia and the downstream pathways in the release of sEng. Methods and Results-Under hypoxic conditions, the trophoblast-like cell line JAR showed an increase in sEng parallel to an elevated formation of reactive oxygen species. Because reactive oxygen species are related to the formation of oxysterols, we assessed the effect of 22-(R)-hydroxycholesterol, a natural ligand of the liver X receptor (LXR), and the LXR synthetic agonist T0901317. Treatment of JAR cells or human placental explants with 22-(R)-hydroxycholesterol or T0901317 resulted in a clear increase in sEng that was dependent on LXR. These LXR agonists induced an increased matrix metalloproteinase-14 expression and activity and a significant reduction of its endogenous inhibitor, tissue inhibitor of metalloproteinase-3. In addition, mice treated with LXR agonists underwent an increase in the plasma sEng levels, concomitant with an increase in arterial pressure. Moreover, transgenic mice overexpressing sEng displayed high blood pressure. Finally, administration of an endoglin peptide containing the consensus matrix metalloproteinase-14 cleavage site G-L prevented the oxysterol-dependent increase in arterial pressure and sEng levels in mice. Conclusions-These studies provide a clue to the involvement of the LXR pathway in sEng release and its pathogenic role in vascular disorders such as preeclampsia. (Circulation. 2012;126:2612-2624.)Key Words: cell hypoxia Ⅲ hypertension Ⅲ pre-eclampsia Ⅲ pregnancy Ⅲ peptides P reeclampsia is a pregnancy-specific syndrome characterized by systemic hypertension, proteinuria, and edema in the third trimester of pregnancy. 1,2 It affects both the fetus and the mother and occurs in Ϸ5% of pregnancies. Severe preeclampsia leads to the appearance of the HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets), seizures, or fetal growth restriction and can result in fetal death. Preeclampsia is thought to be the consequence of impaired placentation resulting from inadequate trophoblastic invasion of the maternal spiral arteries. 3 Abnormal placentation is an important predisposing factor for preeclampsia, whereas endothelial dysfunction appears to be central to the pathophysiological changes, possibly indicative of a 2-stage disorder characterized by reduced placental perfusion and a maternal syndrome. Hypoxia, followed by oxidative stress, has been postulated as a critical signal that initiates the pathogenic process in preeclampsia. 4,5 Hypoxia and extracellular inflammatory signals can induce the intracellular accumulation of reactive oxygen species (ROS). 6,7 In turn, the imbalance between ROS production and antioxidant systems induces oxidative stress that negatively affects reproductive processes, including cyclic luteal and endometrial changes, follicular d...

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“…We used JEG‐3 cells because we previously investigated angiogenic and antiangiogenic factors in these cells …”

Section: Methodsmentioning

confidence: 69%