Preeclampsia: An endothelial cell disorder

Roberts, James C.; Taylor, R. N.; Musci, Thomas J.; Rodgers, George M.; Hubel, Carl A.; McLaughlin, Margaret K.

doi:10.1016/0020-7292(90)90402-7

Cited by 291 publications

(372 citation statements)

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“…There is overwhelming evidence linking pre-eclampsia with the development of endothelial dysfunction (Roberts et al, 1989;McCarthy et al, 1993;Roberts & Redman, 1993;Friedman et al, 1995;Ashworth et al, 1997;Kenny et al, 2002). However, the cellular mechanisms involved have yet to be established.…”

Section: Discussionmentioning

confidence: 99%

“…This stimulates the release of circulating factors that lead to maternal vascular dysfunction (Ashworth et al, 1998). Many studies have shown that the maternal vascular endothelium is the ultimate target of these factors and there is incontrovertible evidence that the normal protective role of this cell layer becomes compromised in pre-eclampsia (Roberts et al, 1989;McCarthy et al, 1993;Roberts & Redman, 1993;Friedman et al, 1995;Ashworth et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

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Excessive stimulation of poly(ADP‐ribosyl)ation contributes to endothelial dysfunction in pre‐eclampsia

Crocker

Kenny

Thornton

et al. 2005

British J Pharmacology

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1 Pre-eclampsia is a serious pregnancy disorder associated with widespread activation of the maternal vascular endothelium. Recent evidence implicates a role for oxidative stress in the aetiology of this condition. 2 Reactive oxygen species, particularly superoxide anions, invokes endothelial cell activation through many pathways. Oxidant-induced cell injury triggers the activation of nuclear enzyme poly(ADP-ribose) polymerase (PARP) leading to endothelial dysfunction in various pathophysiological conditions (reperfusion, shock, diabetes). 3 We have studied whether the loss of endothelial function in pre-eclampsia is dependent on PARP activity. Endothelium-dependent responses of myometrial arteries were tested following exposure to either plasma from women with pre-eclampsia or normal pregnant women in the presence and absence of a novel potent inhibitor of PARP, PJ34. Additional effects of plasma and PJ34 inhibition were identified in microvascular endothelial cell cultures. 4 In myometrial arteries, PARP inhibition blocked the attenuation of endothelium-dependent responses following exposure to plasma from women with pre-eclampsia. In endothelial cell cultures, plasma from pre-eclamptics induced measurable oxidative stress and a concomitant increase in PARP activity and reduction in cellular ATP. Again, these biochemical changes were reversed by PJ34. 5 These results suggest that PARP activity plays a pathogenic role in the development of endothelial dysfunction in pre-eclampsia and promotes PARP inhibition as a potential therapy in this condition.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Excessive stimulation of poly(ADP‐ribosyl)ation contributes to endothelial dysfunction in pre‐eclampsia

Crocker

Kenny

Thornton

et al. 2005

British J Pharmacology

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“…Many investigators believe that preeclampsia is the result of vasoactive and inflammatory mediators secreted by the placenta acting on the vascular endothelium leading to vasoconstriction of the smooth muscle [1,2]. These mediators are likely secreted from trophoblast cells (TCs) in response to placental hypoxia/ischemia and shallow cytotrophoblast invasion acting on vascular endothelium [3].…”

Section: Introductionmentioning

confidence: 99%

Vasoreactivity of Chorionic Plate Arteries in Response to Vasoconstrictors Produced by Preeclamptic Placentas

2007

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Inadequate blood flow and increased vasoconstriction of the placenta contribute to pregnancy associated disorders such as preeclampsia (PE). Because placental vessels lack autonomic innervation, humoral effects of the placenta must play critical roles in regulation of fetal-placental vascular contractility. In this study, we examined the nature of humoral factors produced by PE trophoblasts on placental vessel contractility using an organ bath perfusion model. Vasomotor responses were studied in vitro using placental chorionic plate arteries. Vessel rings from third branch chorionic plate arteries were dissected from human placentas following normal or PE delivery. The arterial rings were equilibrated in Krebs Henseleit buffer and exposed to placental conditioned medium, which was prepared by culture of villous tissue from PE placentas. Receptor antagonists for angiotensin II (ANG II), thromboxane (TX), and endothelin (ET) were used to determine which humoral factor produced by placental tissue (trophoblasts) was more effective in promoting vasoconstriction. The role of angiotensin converting enzyme (ACE) and non-ACE ANG II generating enzymes in regulation of placental vasomotor tone were also investigated. A total of 80 arterial rings from 48 placentas were studied. Our results showed: 1) enhanced vasomotor tone in arteries from PE placentas compared to those from normal placentas; 2) PE-CM induced vaso-constrictive activity could be partially attenuated by receptor antagonists for TX, ANG II and ET, respectively; and 3) chymostatin (a chymase inhibitor) produced a stronger inhibitory effect than captopril (ACE inhibitor) on PE conditioned medium induced vasoconstriction. Our data demonstrate increased vasocontractility in PE placentas and suggest that the non-ACE pathway is probably a major source of ANG II produced in the human placenta.

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“…It has been suggested that failure of trophoblast invasion of the maternal placental bed may be responsible for impaired placental perfusion (Dekker and Sibai, 1998;Patrick and Roberts, 1999). Another key feature of preeclampsia is that endothelial cells are observed to be disrupted histologically (Khong et al, 1992) and functionally (Roberts, 1999); since endothelium has an essential role in the maintenance of a low vascular resistance in normal pregnancy through the release of several vasoactive agents, an abnormal endothelial function in preeclampsia could contribute to an increase in vascular resistance (Roberts et al, 1989).…”

Section: Am In Gestational Pathologiesmentioning

confidence: 99%

Adrenomedullin in mammalian embryogenesis

Garayoa

Bodegas

Cuttitta

et al. 2002

Microscopy Res & Technique

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Here are summarized data supporting that adrenomedullin (AM) is a multifunctional factor involved in the complex regulatory mechanisms of mammalian development. During rodent embryogenesis, AM is first expressed in the heart, followed by a broader but also defined spatio-temporal pattern of expression in vascular, neural, and skeletal-forming tissues as well as in the main embryonic internal organs. AM pattern of expression is suggestive of its involvement in the control of embryonic invasion, proliferation, and differentiation processes, probably through autocrine or paracrine modes of action. AM levels in fetoplacental tissues, uterus, maternal and umbilical plasma are highly increased during normal gestation. These findings in addition to other physiological and gene targeting studies support the importance of AM as a vasorelaxant factor implicated in the regulation of maternal vascular adaptation to pregnancy, as well as of fetal and fetoplacental circulations. AM is also present in amniotic fluid and milk, which is suggestive of additional functions in the maturation and immunological protection of the fetus. Altered expression of AM has been found in some gestational pathologies, although it is not yet clear whether this corresponds to causative or compensatory mechanisms. Future studies in regard to the distribution and expression levels of the molecules known to function as AM receptors, together with data on the action of complement factor H (an AM binding protein), may help to better define the roles of AM during embryonic development.

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Preeclampsia: An endothelial cell disorder

Cited by 291 publications

References 0 publications

Excessive stimulation of poly(ADP‐ribosyl)ation contributes to endothelial dysfunction in pre‐eclampsia

Excessive stimulation of poly(ADP‐ribosyl)ation contributes to endothelial dysfunction in pre‐eclampsia

Vasoreactivity of Chorionic Plate Arteries in Response to Vasoconstrictors Produced by Preeclamptic Placentas

Adrenomedullin in mammalian embryogenesis

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