Hypoxia and sFlt-1 in Preeclampsia: The “Chicken-and-Egg” Question

Karumanchi, S. Ananth; Bdolah, Yuval

doi:10.1210/en.2004-1028

Cited by 180 publications

(127 citation statements)

References 39 publications

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Section: Angiogenic Factorsmentioning

confidence: 99%

“…[73][74][75][76][77][78][79][80] Both plasma and amniotic fluid concentrations of sFlt-1 are increased in preeclamptic patients, as well as placental sFlt-1 mRNA. [73][74][75][76][77][78][79][80] Recently, studies have reported that increased sFlt-1 may have a predictive value in diagnosing preeclampsia as concentrations seem to increase before manifestation of overt symptoms (eg, hypertension, proteinuria). 73,[81][82][83][84] In an elegantly designed study reported several years ago, Maynard et al 85 reported that exogenous administration of sFlt-1 into pregnant rats via adenovirus mediated gene transfer resulted in increased arterial pressure and proteinuria, and decreased plasma free VEGF and PlGF concentrations similar to that observed in the preeclamptic patients.…”

Section: Angiogenic Factorsmentioning

confidence: 99%

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Recent Progress Toward the Understanding of the Pathophysiology of Hypertension During Preeclampsia

2008

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Section: Angiogenic Factorsmentioning

confidence: 99%

Section: Angiogenic Factorsmentioning

confidence: 99%

Recent Progress Toward the Understanding of the Pathophysiology of Hypertension During Preeclampsia

2008

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“…Oxidative stress triggers placental apoptosis, 74 causing the release of microvillous particles containing oxidized lipids, which can then act systemically. The growth factor inhibitor s-Flt is increased with hypoxia, 75 which, when accompanied by reperfusion, can also increase the generation of free radicals.…”

Section: The Linkage Of Stages 1 Andmentioning

confidence: 99%

Preeclampsia

2005

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Abstract-Preeclampsia is a pregnancy complication with serious consequences for mother and infant. The disorder is diagnosed by gestational hypertension and proteinuria but is far more than pregnancy induced hypertension. Preeclampsia is proposed to occur in 2 stages. Key Words: preeclampsia Ⅲ hypertension, pregnancy Ⅲ oxidative stress Ⅲ endothelium P reeclampsia is a pregnancy complication recognized by new-onset gestational hypertension and proteinuria (see definitions below). The disorder affects both mothers and their infants. Once the disease is evident clinically, it can be cured only by delivery. In developed countries, surveillance for preeclampsia through prenatal care allows for early identification and intervention via delivery. This management has changed little in the last 100 years, and it is very effective at reducing maternal mortality. However, maternal morbidity remains great with preeclampsia, which continues to be one of the leading causes for the admission of pregnant women to intensive care units in the developed world. 1 Furthermore, fetal mortality and morbidity is considerable, related to the effects of the disease on the fetus as well as prematurity. The indicated delivery of women to prevent the progression of preeclampsia is responsible for 15% of all preterm births. 2 In developing countries, where inadequate prenatal care limits preeclampsia surveillance, maternal mortality is common, accounting for 50 000 deaths yearly. 3 The hypertensive disorders of pregnancy include hypertension that antedates pregnancy, chronic hypertension, and gestational hypertension occurring uniquely during pregnancy. When the gestational hypertension is accompanied by new-onset proteinuria, the disorder is termed preeclampsia, and when not associated with proteinuria, transient hypertension of pregnancy. If the woman with chronic hypertension also manifests evidence of preeclampsia, this is classified chronic hypertension with superimposed preeclampsia. Eclampsia is the occurrence of seizures in women with preeclampsia. 4 These criteria have been extraordinarily useful to aid in recognizing pregnant women at risk. Greatest risk for mother and baby is present with preeclampsia, and the risk for chronic hypertensive pregnancy is primarily with superimposed preeclampsia. However, the attention to hypertension has, for many years, limited research attention to primarily mechanisms of hypertension. This has not been helpful. In the last 2 decades, appreciation that preeclampsia is a multisystemic syndrome characterized by vasoconstriction, metabolic changes, endothelial dysfunction, activation of the coagulation cascade, and increased inflammatory response, to mention only some of the organ systems involved, has redirected research. 5 As a result, progress in understanding the disorder has accelerated greatly, with attendant optimism for potentially effective treatments. 5 In this article, we consider this recent progress and its clinical implications.

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“…3 It is now generally accepted that preeclampsia starts with inadequate cytotrophoblast invasion and leads to widespread maternal endothelial dysfunction. 4 Recent studies suggest that dysregulation of angiogenic factors and their soluble fmslike tyrosine kinase-1 receptors (sFlt-1) has an important role in the pathogenesis of preeclampsia, but the results are inconsistent. Although some studies report lower plasma vascular endothelial growth factor (VEGF) levels 5 in preeclamptic women compared with normotensive women, [6][7][8][9] other studies report higher levels in preeclamptic women, 10,11 and some found no difference between the two groups.…”

Section: Introductionmentioning

confidence: 99%

Circulating angiogenic factors and their association with birth outcomes in preeclampsia

et al. 2010

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This study was designed to test the hypothesis that altered angiogenic factors together with increased oxidative stress and reduced docosahexaenoic acid (DHA) levels may be associated with altered birth outcome parameters. To test this hypothesis, levels of plasma vascular endothelial growth factor (VEGF), placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1), the oxidative stress marker malondialdehyde (MDA) and fatty acids were estimated in women with preeclampsia and their cord samples and compared with those in normotensive women. The association of these parameters with birth outcome was also examined. Our results show that in preeclamptic women, maternal plasma VEGF and PlGF levels were lower, whereas sFlt-1 levels were higher (Po0.05 for all) than in normotensive women. In contrast, cord plasma VEGF levels were higher (Po0.05) in preeclamptic women, whereas there was no difference in sFlt-1 levels. Plasma DHA levels in both the mother and cord were lower (Po0.05) in the preeclamptic group compared with normotensive women. Maternal plasma sFlt-1 levels were positively (n¼23, r¼0.415, P¼0.039) associated with MDA concentrations in preeclamptic women. Maternal plasma sFlt-1 levels showed a strong negative association with baby weight (n¼37, r¼À0.547, P¼0.001), head circumference (n¼37, r¼À0.472, P¼0.005) and baby chest circumference (n¼37, r¼À0.375, P¼0.032) in the preeclamptic group. Cord plasma sFlt-1 concentrations were negatively associated with cord plasma DHA concentrations (n¼28, r¼À0.552, P¼0.004). This study suggests that dysregulation of angiogenic factors may be associated with maternal oxidative stress. Increased oxidative stress may reduce cord DHA levels and increase sFlt-1 levels, leading to poor birth outcomes in preeclampsia.

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Hypoxia and sFlt-1 in Preeclampsia: The “Chicken-and-Egg” Question

Cited by 180 publications

References 39 publications

Recent Progress Toward the Understanding of the Pathophysiology of Hypertension During Preeclampsia

Recent Progress Toward the Understanding of the Pathophysiology of Hypertension During Preeclampsia

Preeclampsia

Circulating angiogenic factors and their association with birth outcomes in preeclampsia

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