Pre‐eclampsia: fitting together the placental, immune and cardiovascular pieces

James, Joanna L.; Whitley, Guy; Cartwright, Judith E.

doi:10.1002/path.2719

Cited by 195 publications

(136 citation statements)

References 225 publications

(211 reference statements)

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“…Although pregnancy-induced hypertension (PIH) is associated with FGR, FGR also occurs in B8-14% of women without hypertensive disorders. 2,3 Little is known regarding whether pre-HT range pressures impact pregnancy outcomes in the absence of PIH. 4 In this context, blood pressure (BP) in the pre-HT range may be a risk factor for FGR.…”

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confidence: 99%

Blood pressure measurements within the JNC7 pre-hypertensive range after 32 weeks of gestation are a risk factor for decreased fetal growth

et al. 2011

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confidence: 99%

Blood pressure measurements within the JNC7 pre-hypertensive range after 32 weeks of gestation are a risk factor for decreased fetal growth

et al. 2011

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“…Early-onset severe PE (sPE, ≤ 34 wk) is associated with a high incidence of eclampsia, cerebrovascular complications, and fetal growth restriction, which severely threaten maternal and fetal health (1). Although the etiology of PE remains elusive, this disease has two known stages: In stage I, inadequate cytotrophoblast (CTB) invasion early in the pregnancy causes abnormal placentation; in stage II, systemic endothelial cell activation and clinical manifestations occur in the second or third trimester (TM), which are associated with the release of molecules and factors from the shallowly implanted placenta (2,3).…”

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confidence: 99%

Up-regulation of CD81 inhibits cytotrophoblast invasion and mediates maternal endothelial cell dysfunction in preeclampsia

Shen

Diao

Sun

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Preeclampsia (PE) is initiated by abnormal placentation in the early stages of pregnancy, followed by systemic activation of endothelial cells of the maternal small arterioles in the late second or third trimester (TM) of pregnancy. During normal pregnancy, placental cytotrophoblasts (CTBs) invade the maternal uterine wall and spiral arteries, whereas this process is interrupted in PE. However, it is not known how the malformed placenta triggers maternal endothelial crisis and the associated manifestations. Here, we have focused on the association of CD81 with PE. CD81, a member of the tetraspanin superfamily, plays significant roles in cell growth, adhesion, and motility. The function of CD81 in human placentation and its association with pregnancy complications are currently unknown. In the present study, we have demonstrated that CD81 was preferentially expressed in normal first TM placentas and progressively downregulated with gestation advance. In patients with early-onset severe PE (sPE), CD81 expression was significantly up-regulated in syncytiotrophoblasts (STBs), CTBs and the cells in the villous core. In addition, high levels of CD81 were observed in the maternal sera of patients with sPE. Overexpressing CD81 in CTBs significantly decreased CTB invasion, and culturing primary human umbilical vein endothelial cells (HUVECs) in the presence of a high dose of exogenous CD81 resulted in interrupted angiogenesis and endothelial cell activation in vitro. Importantly, the phenotype of human PE was mimicked in the CD81-induced rat model.is characterized by a new onset of hypertension and proteinuria after 20 wk of gestation. Early-onset severe PE (sPE, ≤ 34 wk) is associated with a high incidence of eclampsia, cerebrovascular complications, and fetal growth restriction, which severely threaten maternal and fetal health (1). Although the etiology of PE remains elusive, this disease has two known stages: In stage I, inadequate cytotrophoblast (CTB) invasion early in the pregnancy causes abnormal placentation; in stage II, systemic endothelial cell activation and clinical manifestations occur in the second or third trimester (TM), which are associated with the release of molecules and factors from the shallowly implanted placenta (2, 3).CD81 is a widely expressed tetraspanin that provides a scaffold for signaling molecules and orchestrates interactions between membrane-associated proteins to initiate signaling cascades that regulate cell adhesion, migration, and invasion (4-7). CD81 is also a tumor suppressor that inhibits the migration and invasion of some malignant tumor cells (8, 9). In addition, an increasing number of studies have reported that CD81 is one of the main components of exosomes and can be released into maternal circulation or delivered to certain organs and tissues (10-12). Our previous study showed that CD81 is highly expressed in LPS-treated HTR-8/SV neo cells derived from human first TM extravillous trophoblast cells and induces trophoblast syncytialization (13); however, the role of CD81 in ...

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“…It is thought that an underperfused placenta is responsible for the release of placental debris and multiple factors, which, in turn, causes the maternal syndrome. 3,4 Indeed, preeclampsia has been associated with both increased systemic vascular resistance and endothelial dysfunction.…”

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Lectin-Like Oxidized Low-Density Lipoprotein 1 Receptor in a Reduced Uteroplacental Perfusion Pressure Rat Model of Preeclampsia

et al. 2012

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Abstract-Preeclampsia is a major cause of maternal and fetal morbidity and mortality that has been associated with endothelial dysfunction attributed, in part, to dyslipidemia, an imbalance in angiogenic factors and oxidative stress. One of the many factors that have been shown to be elevated in women with preeclampsia is low-density lipoprotein (LDL) and the more oxidizable, small dense LDL, which can lead to increased vascular oxidative stress and decreased bioavailability of NO. Lectin-like oxidized LDL-1 receptor (LOX-1) is a specific receptor for oxidized LDL. We hypothesized that a reduction of placental perfusion using a rat model of reduced uteroplacental perfusion pressure would result in enhanced LOX-1 expression in the maternal vasculature causing impaired vascular endothelial function through the actions of increased superoxide production and decreased NO-mediated vasodilation. We demonstrated a significant increase in the expression of the LOX-1 receptor (4.3-fold; Pϭ0.002), endothelial NO synthase (2.7-fold; Pϭ0.001), and superoxide (Pϭ0.02) in thoracic aorta of the reduced uteroplacental perfusion pressure model, whereas maximal vasodilator function was modestly decreased (PϽ0.05). Endothelial-dependent vasodilator function was unaffected by either oxidized LDL or an LOX-1 receptor inhibitor in controls but was modestly increased in the presence of both oxidized LDL and the LOX-1 receptor inhibitor in reduced uteroplacental perfusion pressure (Pϭ0.03). In summary, we have shown that, in a rat model of preeclampsia, there is a dramatic increase in the expression levels of both the LOX-1 receptor and the endothelial NO synthase enzyme, along with evidence of increased superoxide production and subsequent modestly decreased endothelial function. (Hypertension. 2012;59:1014-1020.)Key Words: preeclampsia Ⅲ vascular function Ⅲ LOX-1 receptor Ⅲ oxidized LDL Ⅲ RUPP P reeclampsia is one of the most enduring and inadequately understood pathologies of pregnancy, which affects 5% to 8% of pregnancies and is a major cause of maternal and fetal morbidity and mortality.1,2 This almost uniquely human disorder is characterized by de novo hypertension Ͼ140/90 mm Hg after the 20th week of gestation accompanied by proteinuria more than ϩ2. Although the diagnosis is reasonably clear, the underlying causes remain obscure, likely because of the extreme complexity of this disorder. Interestingly, the only currently known cure for preeclampsia is removal of the placenta and, hence, delivery of the baby, suggesting a central role for this organ. It is thought that an underperfused placenta is responsible for the release of placental debris and multiple factors, which, in turn, causes the maternal syndrome.3,4 Indeed, preeclampsia has been associated with both increased systemic vascular resistance and endothelial dysfunction.One of the many factors that have been shown to be elevated in women with preeclampsia is low-density lipoprotein (LDL) and the more oxidizable, small dense LDL. 5-10Combined with a significant volume ...

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Pre‐eclampsia: fitting together the placental, immune and cardiovascular pieces

Cited by 195 publications

References 225 publications

Blood pressure measurements within the JNC7 pre-hypertensive range after 32 weeks of gestation are a risk factor for decreased fetal growth

Blood pressure measurements within the JNC7 pre-hypertensive range after 32 weeks of gestation are a risk factor for decreased fetal growth

Up-regulation of CD81 inhibits cytotrophoblast invasion and mediates maternal endothelial cell dysfunction in preeclampsia

Lectin-Like Oxidized Low-Density Lipoprotein 1 Receptor in a Reduced Uteroplacental Perfusion Pressure Rat Model of Preeclampsia

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