A potential pathophysiological role for galectins and the renin–angiotensin system in preeclampsia

Blois, Sandra M.; Dechend, Ralf; Barrientos, Gabriela; Staff, Anne Cathrine

doi:10.1007/s00018-014-1713-1

Cited by 14 publications

(7 citation statements)

References 108 publications

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“…Thus, the eCTB subpopulation might play a role in the dysregulation of the renin-angiotensin system that is observed in preeclampsia. 73 This category of differential expression genes also included CHI3L1 (a glycosidase that is an important modulator of the tumor microenvironment), 74 VTRNA2-1 (which plays important roles in apoptosis), 75 HMOX1, and KDR (VEGFR-2), which we previously showed was down-regulated as cytotrophoblasts differentiate along the invasive pathway. 30 Its up-regulation in the context of sPE is consistent with deficits in eCTB differentiation.…”

Section: Gsta3mentioning

confidence: 99%

“…A great deal of work over many decades has gone into investigating the role of the circulating reninangiotensin system in preeclampsia. 73 The renin-angiotensin system, which plays a major role in regulating blood pressure, 104 is dysregulated in hypertension. Patients with preeclampsia have lower plasma renin levels 105,106 and higher sensitivity to angiotensin II, 107,108 which predates the appearance of the signs of this pregnancy complication.…”

Section: Research Implicationsmentioning

confidence: 99%

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Preeclampsia: novel insights from global RNA profiling of trophoblast subpopulations

Gormley

Ona

Kapidzic

et al. 2017

American Journal of Obstetrics and Gynecology

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BACKGROUND:The maternal signs of preeclampsia, which include the new onset of high blood pressure, can occur because of faulty placentation. We theorized that transcriptomic analyses of trophoblast subpopulations in situ would lend new insights into the role of these cells in preeclampsia pathogenesis. OBJECTIVE: Our goal was to enrich syncytiotrophoblasts, invasive cytotrophoblasts, or endovascular cytotrophoblasts from the placentas of severe preeclampsia cases. Total RNA was subjected to global transcriptional profiling to identify RNAs that were misexpressed compared with controls. STUDY DESIGN: This was a cross-sectional analysis of placentas from women who had been diagnosed with severe preeclampsia. Gestational age-matched controls were placentas from women who had a preterm birth with no signs of infection. Laser microdissection enabled enrichment of syncytiotrophoblasts, invasive cytotrophoblasts, or endovascular cytotrophoblasts. After RNA isolation, a microarray approach was used for global transcriptional profiling. Immunolocalization identified changes in messenger RNA expression that carried over to the protein level. Differential expression of noneprotein-coding RNAs was confirmed by in situ hybridization. A 2-way analysis of variance of non-coding RNA expression identified particular classes that distinguished trophoblasts in cases vs controls. Cajal body foci were visualized by coilin immunolocalization. RESULTS: Comparison of the trophoblast subtype data within each group (severe preeclampsia or noninfected preterm birth) identified many highly differentially expressed genes. They included molecules that are known to be expressed by each subpopulation, which is evidence that the method worked. Genes that were expressed differentially between the 2 groups, in a cell-typeespecific manner, encoded a combination of molecules that previous studies associated with severe preeclampsia and those that were not known to be dysregulated in this pregnancy

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Section: Gsta3mentioning

confidence: 99%

Section: Research Implicationsmentioning

confidence: 99%

Preeclampsia: novel insights from global RNA profiling of trophoblast subpopulations

Gormley

Ona

Kapidzic

et al. 2017

American Journal of Obstetrics and Gynecology

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“…In 2005, Redman proposed two stages of preeclampsia [9] and that model has persisted with modifications to guide our understanding of the disorder [10, 11]. In Stage 1 of preeclampsia (pre-clinical) which occurs in the first half of pregnancy, defective placentation occurs resulting in placental ischemia and release of placental factors into the maternal circulation.…”

Section: Introductionmentioning

confidence: 99%

The Complement System and Preeclampsia

2017

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Purpose of review Preeclampsia affects 3–4% of pregnancies with few treatment options to reduce maternal and fetal harm. Recent evidence that targeting the complement system may be an effective therapeutic strategy in prevention or treatment of preeclampsia will be reviewed. Recent findings Studies in humans confirm the safety and efficacy of C5 blockade in complement-mediated disorders of pregnancy, including preeclampsia. Animal models mimic the placental abnormalities, and/or the maternal symptoms, which characterize preeclampsia. These models in mouse and rat have defined a role for complement and its regulators in placental dysfunction, hypertension, proteinuria, endothelial dysfunction, fetal growth restriction and angiogenic imbalance, thus informing future human studies. Summary Targeting excessive complement activation, particularly the terminal complement complex (C5b-9) and C5a may be an effective strategy to prolong pregnancy in women with preeclampsia. Continued research is needed to identify the initiator(s) of activation, the pathways involved and the key component(s) in the pathophysiology to allow development of safe and effective therapeutics to target complement without compromising its role in homeostasis and host defense.

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“…A recent cross-sectional study showed that urinary angiotensinogen/creatinine ratio was correlated with high blood pressure and proteinuria in preeclampsia ( Yilmaz et al, 2015 ). The renin-angiotensin system has also been implicated in the pathogenesis of preeclampsia ( Verdonk et al, 2014 ; Blois et al, 2015 ). However, the results of investigations on the significance of the renin-angiotensin system in gestational diabetes and preeclampsia have been contentious ( Gathiram and Moodley, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Urinary Angiotensinogen-Melatonin Ratio in Gestational Diabetes and Preeclampsia

Valias

Gomes

Amaral

et al. 2022

Front. Mol. Biosci.

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Background: A large research portfolio indicates that an activated renal renin-angiotensin system or a deficit on melatonin is associated with several cardiovascular pathologies. In this observational clinical study, we hypothesized that alterations in urinary melatonin or angiotensinogen levels may be altered in two common conditions, preeclampsia and gestational diabetes. Our study’s primary objective was to assess melatonin and angiotensinogen as novel disease biomarkers detectable and quantifiable in the urine of pregnant women with or without pregnancy complications.Methods: This was a concurrent cohort study of pregnant women with selected obstetric pathologies (gestational diabetes, preeclampsia, hypertension and obesity with hypertension). A group of healthy controls was also included. Urinary 6-sulfatoxymelatonin and angiotensinogen were measured by sensitive and specific ELISAs in first morning void urine samples. The patients were included in the cohort consecutively, and the diagnosis was blinded at the level of urine collection. Urinary 6-sulfatoxymelatonin and angiotensinogen levels were investigated in the patients included in the cohort.Results: Urinary levels of angiotensinogen were significantly higher in the gestational diabetes [angiotensinogen/creatinine ratio median (25th, 75th): 0.11 (0.07, 0.18)] and preeclampsia [0.08 (0.06, 0.18)] groups than in those with healthy pregnancy [0.05(0.04, 0.06]; 6-sulfatoxymelatonin levels were significantly lower in the gestational diabetes [ug/h: median (25th, 75th): 0.12(0.08, 0.17)] and preeclampsia [0.12 (0.09, 0.15)] groups than in those with healthy pregnancy [0.20 (0.15, 0.27]. Neither morning void protein/creatinine ratio nor 24-h urine protein estimate were significantly different between the study groups.Conclusion: These results suggest that urinary angiotensinogen levels may indicate an intrarenal RAS activation while melatonin production appears to be defective in gestational diabetes or hypertension. An angiotensinogen/melatonin ratio is suggested as an early biomarker for identification of gestational diabetes or hypertension. This report provides a basis for the potential use of melatonin for the treatment of preeclampsia. A prospective study in a larger number of patients to determine the operative characteristics of these markers as potential diagnostic tests is justified.

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A potential pathophysiological role for galectins and the renin–angiotensin system in preeclampsia

Cited by 14 publications

References 108 publications

Preeclampsia: novel insights from global RNA profiling of trophoblast subpopulations

Preeclampsia: novel insights from global RNA profiling of trophoblast subpopulations

The Complement System and Preeclampsia

Urinary Angiotensinogen-Melatonin Ratio in Gestational Diabetes and Preeclampsia

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