New Developments in the Pathogenesis of Preeclampsia

Naljayan, Mihran; Karumanchi, S. Ananth

doi:10.1053/j.ackd.2013.02.003

Cited by 83 publications

(71 citation statements)

References 87 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…As hypertension and preexisting renal disease are strong risk factors for the development of preeclampsia, we hypothesized that this model would develop superimposed preeclampsia during pregnancy. In addition, the Dahl S rat has impaired nitric oxide production (9, 10, 43), increased oxidative stress (27,47,48), and immune activation (24,28), all of which are factors proposed to contribute to the pathogenesis of preeclampsia (29). Indeed, we observed that the Dahl S rat does exhibit worsening hypertension in late pregnancy, in contrast to both the normotensive SD and the hypertensive SHR.…”

Section: R65mentioning

confidence: 70%

The Dahl salt-sensitive rat is a spontaneous model of superimposed preeclampsia

Gillis¹,

Williams²,

Garrett

et al. 2015

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

The Dahl salt-sensitive rat is a spontaneous model of superimposed preeclampsia. Am J Physiol Regul Integr Comp Physiol 309: R62-R70, 2015. First published April 22, 2015 doi:10.1152/ajpregu.00377.2014.-The mechanisms of the pathogenesis of preeclampsia, a leading cause of maternal morbidity and death worldwide, are poorly understood in part due to a lack of spontaneous animal models of the disease. We hypothesized that the Dahl salt-sensitive (S) rat, a genetic model of hypertension and kidney disease, is a spontaneous model of superimposed preeclampsia. The Dahl S was compared with the Sprague-Dawley (SD) rat, a strain with a well-characterized normal pregnancy, and the spontaneously hypertensive rat (SHR), a genetic model of hypertension that does not experience a preeclamptic phenotype despite preexisting hypertension. Mean arterial pressure (MAP, measured via telemetry) was elevated in the Dahl S and SHR before pregnancy, but hypertension was exacerbated during pregnancy only in Dahl S. In contrast, SD and SHR exhibited significant reductions in MAP consistent with normal pregnancy. Dahl S rats exhibited a severe increase in urinary protein excretion, glomerulomegaly, increased placental hypoxia, increased plasma soluble fms-like tyrosine kinase-1 (sFlt-1), and increased placental production of tumor necrosis factor-␣ (TNF-␣). The Dahl S did not exhibit the expected decrease in uterine artery resistance during late pregnancy in contrast to the SD and SHR. Dahl S pups and litter sizes were smaller than in the SD. The Dahl S phenotype is consistent with many of the characteristics observed in human superimposed preeclampsia, and we propose that the Dahl S should be considered further as a spontaneous model to improve our understanding of the pathogenesis of superimposed preeclampsia and to identify and test new therapeutic targets for its treatment.pregnancy; hypertension; proteinuria; uterine artery resistance; animal model; superimposed preeclampsia; TNF-␣; HIF-1␣; sFLT-1 PREECLAMPSIA is characterized by hypertension, proteinuria, and endothelial dysfunction after the twentieth week of pregnancy. Preeclampsia is currently among the leading causes of maternal morbidity and death worldwide, affecting approximately 5% of all pregnancies in the United States (35, 38). Preexisting chronic hypertension or chronic kidney disease dramatically increases the risk of developing superimposed preeclampsia during pregnancy, with an estimated 25% of chronically hypertensive women (39) and 30% of women with chronic kidney disease (23) developing superimposed preeclampsia. Furthermore, women with superimposed preeclampsia have an even greater risk of adverse maternal and fetal outcomes compared with women with de novo preeclampsia (8). Despite the severity and incidence of this disease, the mechanisms of the pathogenesis of preeclampsia remain unclear. There is currently no effective treatment available, and the only known "cure" for preeclampsia is the delivery of the placenta. There is also a potential for consequences o...

show abstract

Section: R65mentioning

confidence: 70%

The Dahl salt-sensitive rat is a spontaneous model of superimposed preeclampsia

Gillis¹,

Williams²,

Garrett

et al. 2015

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

show abstract

“…Briefly, the predictive strategy is based on the well-established findings that the stressed placenta is producing increased amounts of the antiangiogenic factor soluble FMS-like tyrosine kinase 1 (sFLT-1) that binds the pro-angiogenic factors in the maternal circulation (mainly vascular endothelial growth factor (VEGF) and placental growth factor (PlGF). This leads to decreased angiogenic stimulation of the endothelium and consequently to endotheliosis [36,37]. Endotheliosis is also present in the kidneys, which leads to glomerular endotheliosis, podocyte injury and eventually proteinuria, hallmarks of PE [38].…”

Section: Biochemical Markersmentioning

confidence: 99%

First Trimester Prediction of Preeclampsia

et al. 2015

View full text Add to dashboard Cite

Preeclampsia (PE) is a serious pregnancy-related condition that causes severe maternal and fetal morbidity and mortality. Within the recent years, there has been an increasing focus in predicting PE at the end of the first trimester of pregnancy. In this review, literature published between 2011 and 2015 was evaluated. In a total of six biomarker algorithms, for first and early second trimester, the prediction of preeclampsia is discussed. In addition, one randomized clinical trial was included. Several algorithms were based on placental biomarkers such as pregnancy-associated plasma protein A (PAPP-A), placental growth factor (PLGF), and soluble FMS-like tyrosine kinase 1 (s-FLT-1). The algorithms containing these biomarkers showed a high prediction rate (PR) for early onset PE, ranging from 44 to 92 % at 5 % false positive rate (FPR). New biomarkers suggest an alternative model based on free HbF and the heme scavenger alpha-1-microglobulin (A1M) with a prediction rate of 69 % at an FPR of 5 %. Interestingly, this model performs well without uterine artery Doppler pulsatility index (UtAD-PI), which is an advantage particularly if the screening method were to be implemented in developing countries. The randomized clinical trial showed a clear reduction in early onset PE as well as reducing preterm PE if identified high-risk pregnancies were treated with low-dose aspirin. In conclusion, PE prediction is now possible through several prediction algorithms and prophylaxis is beneficial in high-risk cases.

show abstract

“…In the past decade, numerous studies have documented altered concentrations of circulating factors (the AT1 activating antibody has already been considered), particularly those derived from the PE placenta. The current knowledge on this topic was recently reviewed [121,122,123] by the authors who pioneered the sFlt-1 theory a decade ago [121,124]. …”

Section: Strategies For Predicting Pe and The Use Of Novel Biomarkersmentioning

confidence: 99%

Preeclampsia and Maternal Cardiovascular Disease: Consequence or Predisposition?

Osol

Bernstein²

2014

J Vasc Res

View full text Add to dashboard Cite

Formerly preeclamptic women stand a higher chance of developing cardiovascular disease (CVD) later in life and may experience a shortened life span. This review updates the pathophysiology and definition of this complex disease and highlights the protective role of pregnancy by considering the relationship between pregnancy interval and likelihood of disease recurrence. The evidence for persistent maternal cardiovascular impairment following preeclampsia (PE) is considered, e.g. postpartum changes in CVD occurrence, blood pressure elevation and changes in the renin-angiotensin-aldosterone system). Since maternal endothelial dysfunction is a hallmark of PE, we summarize the evidence for reduced flow-mediated dilation in women with previous PE, and consider the utility and shortcomings of this clinical measure. In addition to viewing postpartum changes as a consequence of this disease, we consider the alternative view that PE might be the manifestation of a maternal phenotype that already has some predisposition to or is in the earlier stages of CVD; in this case, some of the postpartum residual deficits (or their antecedents) may have already been present prior to pregnancy. Finally, we consider the use of novel biomarkers for predicting or detecting PE prior to the appearance of clinical symptoms.

show abstract

New Developments in the Pathogenesis of Preeclampsia

Cited by 83 publications

References 87 publications

The Dahl salt-sensitive rat is a spontaneous model of superimposed preeclampsia

The Dahl salt-sensitive rat is a spontaneous model of superimposed preeclampsia

First Trimester Prediction of Preeclampsia

Preeclampsia and Maternal Cardiovascular Disease: Consequence or Predisposition?

Contact Info

Product

Resources

About