Decreased circulating anandamide levels in preeclampsia

Molvarec, Attila; Fügedi, Gergely; Szabó, Eszter; Stenczer, Balázs; Walentin, Szilvia; Rigó, János

doi:10.1038/hr.2015.20

Cited by 23 publications

(16 citation statements)

References 52 publications

(51 reference statements)

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“…Our previous study [21,23] confirmed the value of measuring endothelial dysfunction along with arterial stiffness, which on some occasions were also linked to additional cardiovascular disorders. Immunological and inflammatory components are major underlying pathways leading to the development of PE, and some features of this disorder may become systemic later on [42][43][44]. This might also be the reason why low-dose aspirin is less effective in women with previous FGR compared to women with previous PE and may account for the lower efficacy of aspirin in preventing PE in women with chronic hypertension [28][29][30][31].…”

Section: Discussionmentioning

confidence: 99%

Pro- and Anti-Angiogenic Markers as Clinical Tools for Suspected Preeclampsia with and without FGR near Delivery—A Secondary Analysis

et al. 2021

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Objective—the objective of this study was to assess the accuracy of placental growth factor (PlGF), soluble Fms-like Tyrosine Kinase 1 (sFlt-1), and endoglin (sEng) in the diagnosis of suspected preeclampsia (PE) with and without fetal growth restriction (FGR) near delivery. Methods—this is a secondary analysis of a dataset of 125 pregnant women presenting at the high risk pregnancy clinic with suspected PE, FGR or PE + FGR in the University Medical Center of Slovenia. The dataset included 31 PE cases, 16 FGR cases, 42 PE + FGR cases, 15 cases who developed with unrelated complications before 37 weeks (wks) (PTD), and 21 unaffected controls who delivered a healthy baby at term. We also analyzed a sub-group of women who delivered early (<34 wks) including 10 PE, 12 FGR, 28 PE + FGR, and six PTD. Clinical management adhered to hospital guidelines. Marker levels were extracted from the dataset and were used to develop Receiver Operating Characteristic (ROC) curves and to calculate the area under the curve (AUC), the detection rates (DRs), and the false positive rates (FPRs). Previously published marker cutoffs for yes/no admission to hospital wards were extracted from the literature. Negative and positive predictive values (NPVs and PPVs) were evaluated for their value in determining whether hospital admission was required. Non-parametric tests were applied for statistical analysis; p < 0.05 was considered significant. Results—near delivery, all the pro-and anti-angiogenic markers provided diagnostic (ROC = 1.00) accuracy for the early (<34 wks) group of FGR. Diagnostic or near diagnostic (ROC = 0.95) accuracy was achieved by all marker for early PE + FGR but lower accuracy was achieved for early PE. For all cases, all markers, especially PlGF reached diagnostic or near diagnostic accuracy for FGR and PE + FGR. At this accuracy level, they can contribute to the clinical management of FGR, and PE + FGR. All the markers were less accurate for all PE cases. The use of published cutoffs was adequate for clinical management of FGR, whether early or for all cases, using an NPV > 90%. For PE + FGR, the PPV value approached 100%, especially for early cases, and can thus be implemented in clinical management. Neither NPV nor PPV were high enough for managing all cases of PE. There was no added value in measuring the PlGF/(sFlt-1 + sEng) ratio. Conclusion—This is the first study on a Slovenian population. It shows that near-delivery angiogenic biomarkers tests may be useful for confirming the diseases in cases where there is a diagnostic doubt. However, the clinical use of the biomarkers needs to be weighed against resources available and degree of certainty of the diagnosis made with and without them for managing suspected FGR and PE + FGR requiring delivery <34 wks, where they are very accurate, and furthermore in the management of all cases of FGR and FGR+PE. The markers were less accurate for the clinical diagnosis of PE.

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Section: Discussionmentioning

confidence: 99%

Pro- and Anti-Angiogenic Markers as Clinical Tools for Suspected Preeclampsia with and without FGR near Delivery—A Secondary Analysis

et al. 2021

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“…Another study published that CB1 expression was higher in placentas from pregnancies complicated by preeclampsia compared to controls, with no change in CB2 receptor levels (Fugedi, et al, 2014). Contradictory to these data is one study that demonstrated circulating levels of AEA are lower in preeclampsia (Molvarec et al, 2015). Blood AEA concentration, however, is not necessarily an indicator of local AEA concentration or AEA signaling within the placenta and may be under the control of feedback mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Anandamide down-regulates placental transporter expression through CB2 receptor-mediated inhibition of cAMP synthesis

Szilagyi

Composto-Wahler

Joseph

et al. 2019

Pharmacological Research

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The BCRP/ABCG2 efflux transporter is expressed on the membrane of placental syncytiotrophoblasts and protects the fetus from toxicant exposure. Syncytiotrophoblasts arise from the fusion of cytotrophoblasts, a process negatively regulated by the endocannabinoid, anandamide (AEA). It is unknown whether AEA can influence fetal concentrations of xenobiotics by modulating the expression of transporters in syncytiotrophoblasts. Here, we sought to characterize and identify the mechanism(s) responsible for AEA-mediated down-regulation of the BCRP transporter in human placental explants and BeWo trophoblasts. Treatment of human placental explants with AEA (1 μM, 24 h) reduced hCGα, syncytin-1, and BCRP mRNAs by ~30%. Similarly, treatment of BeWo trophoblasts with AEA (0-10 μM, 3-24 h) coordinately downregulated mRNAs for hCGβ, syncytin-2, and BCRP. In turn, AEA increased the sensitivity of trophoblasts to the cytotoxicity of mitoxantrone, a known BCRP substrate, and environmental and dietary contaminants including mycoestrogens and perfluorinated chemicals. AEA-treated

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“…Indeed, increased blood pressure in rats produces an elevation of AEA concentrations in the NTS (Seagard et al, 2004). On the other hand, circulating concentrations of AEA are significantly reduced in individuals with preeclampsia, a condition associated with hypertension in late pregnancy (Molvarec et al, 2015), suggesting that increased blood pressure alone is not sufficient to elevate circulating AEA concentrations.…”

Section: Circulating Endocannabinoids and Chronic Sns Or Hpa Axis Actmentioning

confidence: 99%

Circulating Endocannabinoids: From Whence Do They Come and Where are They Going?

Hillard

2017

Neuropsychopharmacol.

329

241

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The goal of this review is to summarize studies in which concentrations of circulating endocannabinoids in humans have been examined in relationship to physiological measurements and pathological status. The roles of endocannabinoids in the regulation of energy intake and storage have been well studied and the data obtained consistently support the hypothesis that endocannabinoid signaling is associated with increased consumption and storage of energy. Physical exercise mobilizes endocannabinoids, which could contribute to refilling of energy stores and also to the analgesic and mood-elevating effects of exercise. Circulating concentrations of 2-arachidonoylglycerol are very significantly circadian and dysregulated when sleep is disrupted. Other conditions under which circulating endocannabinoids are altered include inflammation and pain. A second important role for endocannabinoid signaling is to restore homeostasis following stress. Circulating endocannabinoids are stress-responsive and there is evidence that their concentrations are altered in disorders associated with excessive stress, including post-traumatic stress disorder. Although determination of circulating endocannabinoids can provide important information about the state of endocannabinoid signaling and thus allow for hypotheses to be defined and tested, the large number of physiological factors that contribute to their circulating concentrations makes it difficult to use them in isolation as a biomarker for a specific disorder.

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Decreased circulating anandamide levels in preeclampsia

Cited by 23 publications

References 52 publications

Pro- and Anti-Angiogenic Markers as Clinical Tools for Suspected Preeclampsia with and without FGR near Delivery—A Secondary Analysis

Pro- and Anti-Angiogenic Markers as Clinical Tools for Suspected Preeclampsia with and without FGR near Delivery—A Secondary Analysis

Anandamide down-regulates placental transporter expression through CB2 receptor-mediated inhibition of cAMP synthesis

Circulating Endocannabinoids: From Whence Do They Come and Where are They Going?

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