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  • 1
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    Online Resource
    Fluid shear stress induces a shift from glycolytic to amino acid pathway in human trophoblasts
    Springer Science and Business Media LLC ; 2023
    In:  Cell & Bioscience Vol. 13, No. 1 ( 2023-09-08)
    Details
    In: Cell & Bioscience, Springer Science and Business Media LLC, Vol. 13, No. 1 ( 2023-09-08)
    Abstract: The human placenta, a tissue with a lifespan limited to the period of pregnancy, is exposed to varying shear rates by maternal blood perfusion depending on the stage of development. In this study, we aimed to investigate the effects of fluidic shear stress on the human trophoblast transcriptome and metabolism. Results Based on a trophoblast cell line cultured in a fluidic flow system, changes caused by shear stress were analyzed and compared to static conditions. RNA sequencing and bioinformatics analysis revealed an altered transcriptome and enriched gene ontology terms associated with amino acid and mitochondrial metabolism. A decreased GLUT1 expression and reduced glucose uptake, together with downregulated expression of key glycolytic rate-limiting enzymes, hexokinase 2 and phosphofructokinase 1 was observed. Altered mitochondrial ATP levels and mass spectrometry data, suggested a shift in energy production from glycolysis towards mitochondrial oxidative phosphorylation. This shift in energy production could be supported by increased expression of glutamic-oxaloacetic transaminase variants in response to shear stress as well as under low glucose availability or after silencing of GLUT1. The shift towards amino acid metabolic pathways could be supported by significantly altered amino acid levels, like glutamic acid, cysteine and serine. Downregulation of GLUT1 and glycolytic rate-limiting enzymes, with concomitant upregulation of glutamic-oxaloacetic transaminase 2 was confirmed in first trimester placental explants cultured under fluidic flow. In contrast, high fluid shear stress decreased glutamic-oxaloacetic transaminase 2 expression in term placental explants when compared to low flow rates. Placental tissue from pregnancies with intrauterine growth restriction are exposed to high shear rates and showed also decreased glutamic-oxaloacetic transaminase 2, while GLUT1 was unchanged and glycolytic rate-limiting enzymes showed a trend to be upregulated. The results were generated by using qPCR, immunoblots, quantification of immunofluorescent pictures, padlock probe hybridization, mass spectrometry and FRET-based measurement. Conclusion Our study suggests that onset of uteroplacental blood flow is accompanied by a shift from a predominant glycolytic- to an alternative amino acid converting metabolism in the villous trophoblast. Rheological changes with excessive fluidic shear stress at the placental surface, may disrupt this alternative amino acid pathway in the syncytiotrophoblast and could contribute to intrauterine growth restriction.
    Type of Medium: Online Resource
    ISSN: 2045-3701
    URL: Article
    DOI: 10.1186/s13578-023-01114-3
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2593367-X
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  • 2
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    Angiogenic growth factors in the diagnosis and prediction of pre-eclampsia
    Portland Press Ltd. ; 2012
    In:  Clinical Science Vol. 122, No. 2 ( 2012-01-01), p. 43-52
    Details
    In: Clinical Science, Portland Press Ltd., Vol. 122, No. 2 ( 2012-01-01), p. 43-52
    Abstract: The pathogenesis of pre-eclampsia is still not completely known; however, in the recent decade, there have been tremendous research efforts leading to impressive results highlighting the role of a disturbed angiogenic balance as one of the key features of the disease. Numerous studies have shown the key role of the placenta in the pathogenesis of pre-eclampsia. A shift in the sFlt-1 (soluble Fms-like tyrosine kinase-1)/PlGF (placental growth factor) ratio is associated with the disease. Although pre-eclampsia seems to be a clearly defined disease, clinical presentation, and particularly the dynamics of the clinical course, can vary enormously. The only available tools to diagnose pre-eclampsia are blood pressure measurement and urine protein sampling. However, these tools have a low sensitivity and specificity regarding the prediction of the course of the disease or maternal and perinatal outcomes. The only cure for the disease is delivery, although a timely diagnosis helps in decreasing maternal and fetal morbidity and mortality. The sFlt1/PlGF ratio is able to give additional valuable information on the status and progression of the disease and is apt to be implemented in the diagnostic algorithm of pre-eclampsia. In the present review, we aim to provide an overview of the vast literature on angiogenesis and anti-angiogenesis factors in pre-eclampsia that have been published over the last decade. We introduce work from basic research groups who have focused on the pathophysiological basis of the disease. Furthermore, we review studies with a clinical focus in which the sFlt-1/PlGF ratio has been analysed along with other candidates for routine clinical assessment of pre-eclampsia.
    Type of Medium: Online Resource
    ISSN: 0143-5221 , 1470-8736
    URL: Article
    DOI: 10.1042/CS20110097
    Language: English
    Publisher: Portland Press Ltd.
    Publication Date: 2012
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  • 3
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    Prediction of Preeclampsia-Related Adverse Outcomes With the sFlt-1 (Soluble fms-Like Tyrosine Kinase 1)/PlGF (Placental Growth Factor)-Ratio in the Clinical Routine : A Real-World Study
    Ovid Technologies (Wolters Kluwer Health) ; 2021
    In:  Hypertension Vol. 77, No. 2 ( 2021-02), p. 461-471
    Details
    In: Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 77, No. 2 ( 2021-02), p. 461-471
    Abstract: This retrospective real-world study investigated the clinical use of the sFlt-1 (soluble fms-like tyrosine kinase 1)/PlGF (placental growth factor) ratio alone or in combination with other clinical tests to predict an adverse maternal (maternal death, kidney failure, hemolysis elevated liver enzymes low platelets-syndrome, pulmonary edema, disseminated intravascular coagulation, cerebral hemorrhage, or eclampsia) or fetal (delivery before 34 weeks because of preeclampsia and/or intrauterine growth restriction, respiratory distress syndrome, necrotizing enterocolitis, intraventricular hemorrhage, placental abruption or intrauterine fetal death or neonatal death within 7 days post natum) pregnancy outcome in patients with signs and symptoms of preeclampsia. We evaluated the sFlt-1/PlGF-ratio cutoff values of 38 and 85 and evaluated its integration into a multimarker model. Of 1117 subjects, 322 (28.8%) developed an adverse fetal or maternal outcome. Patients with an adverse versus no adverse outcome had a median sFlt-1/PlGF-ratio of 177 (interquartile range, 54–362) versus 14 (4–64). Risk-stratification with the sFlt-1/PlGF cutoff values into high- ( 〉 85), intermediate- (38–85), and low-risk ( 〈 38) showed a significantly shorter time to delivery in high- and intermediate- versus low-risk patients (4 versus 8 versus 29 days). When integrating all available clinical information into a multimarker model, an area under the curve of 88.7% corresponding to a sensitivity, specificity, positive and negative predictive value of 80.0%, 87.3%, 75.0%, and 90.2% was reached. The sFlt-1/PlGF-ratio alone was inferior to the full model with an area under the curve of 85.7%. As expected, blood pressure and proteinuria were significantly less accurate with an area under the curve of 69.0%. Combining biomarker measurements with all available information in a multimarker modeling approach increased detection of adverse outcomes in women with suspected disease.
    Type of Medium: Online Resource
    ISSN: 0194-911X , 1524-4563
    URL: Article
    DOI: 10.1161/HYPERTENSIONAHA.120.15146
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
    detail.hit.zdb_id: 2094210-2
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  • 4
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    Angiogenic Markers and Cardiovascular Indices in the Prediction of Hypertensive Disorders of Pregnancy
    Ovid Technologies (Wolters Kluwer Health) ; 2017
    In:  Hypertension Vol. 69, No. 6 ( 2017-06), p. 1192-1197
    Details
    In: Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 69, No. 6 ( 2017-06), p. 1192-1197
    Abstract: Angiogenic and antiangiogenic factors have proven to be an accurate predictive means of preeclampsia. Echocardiographic studies have shown that women with preeclampsia exhibit significant cardiovascular strain, especially early-onset preeclampsia. The aim of this study is to determine preeclampsia risk with soluble fms-like tyrosin kinase 1/placental growth factor ratio, serum NT-proBNP (N-terminal pro B-type natriuretic peptide), and biophysical markers of cardiovascular function in a prospective case–control study. We examined a cohort of 110 pregnant women with uneventful pregnancy outcome (controls) and 129 with hypertensive pregnancy disorders, including 77 with preeclampsia and 52 with pregnancy-induced hypertension. Cardiac indices were obtained with a USCOM-1A monitor, and soluble fms-like tyrosin kinase 1, placental growth factor, and NT-proBNP were measured in serum samples on automated platforms. Logistic regression, as well as Cox proportional hazard analysis, was performed. There were significant contributions from all variables tested, except for heart rate, stroke volume index, and cardiac index to the prediction model. When testing accuracy of respective markers in combination (full model) versus individual markers (soluble fms-like tyrosin kinase 1/placental growth factor ratio and total peripheral resistance) was compared. The soluble fms-like tyrosin kinase 1/placental growth factor ratio and total peripheral resistance performed as good as the full model, except for hypertensive pregnancy disorders and pregnancy-induced hypertension, where the full model performed better. The additional assessment of biophysical and biochemical markers of cardiovascular strain in pregnancy increases the detection of the composite group of hypertensive pregnancy disorders, while not significantly improving detection of preeclampsia alone. This offers a more precise insight into the pathogenesis of the disease, as well as offering a window for intervention, possibly decreasing cardiovascular mortality in these women.
    Type of Medium: Online Resource
    ISSN: 0194-911X , 1524-4563
    URL: Article
    DOI: 10.1161/HYPERTENSIONAHA.117.09256
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2017
    detail.hit.zdb_id: 2094210-2
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  • 5
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    Prevalence of Agonistic Autoantibodies Against the Angiotensin II Type 1 Receptor and Soluble fms-Like Tyrosine Kinase 1 in a Gestational Age–Matched Case Study
    Ovid Technologies (Wolters Kluwer Health) ; 2009
    In:  Hypertension Vol. 53, No. 2 ( 2009-02), p. 393-398
    Details
    In: Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 53, No. 2 ( 2009-02), p. 393-398
    Abstract: We showed earlier that activating autoantibodies against the angiotensin II type 1 (AT 1 ) receptor (AT1-AA) circulate in preeclamptic women. They may be involved in the pathogenesis of preeclampsia. Protein alignment suggests that the binding site for AT1-AAs is highly homologous to the capsid protein VP2 of parvovirus B19. We performed a prospective, nested, case-control study of 30 gestational age–matched women with preeclampsia and 30 normotensive pregnant women. We measured AT1-AA, soluble fms-like tyrosine kinase 1 (sFlt-1), and serum immunoglobulin G against parvovirus B19 proteins. AT1-AAs were present in 70% of preeclamptic patients and absent in 80% of controls. Prediction by AT1-AA was improved in late-onset preeclampsia. The discrimination for sFlt-1 was 96%. We did not find an interaction between sFlt-1 and AT1-AA. A human monoclonal immunoglobulin G antibody against parvovirus B19 VP2-protein showed a positive reaction in the AT1-AA bioassay, which could be blocked by an AT 1 receptor blocker, as well as by the epitope amino acid sequence. Immunoglobulin G against parvovirus B19 proteins was similarly distributed between preeclamptic patients and controls and had no significant importance. We detected significantly more AT1-AA in women with an immune response corresponding with parvovirus B19 infection corresponding with a distant viral infection associated with virus elimination. We concluded that AT1-AAs were common in patients with preeclampsia in a prospective case-control study, although sFlt-1 was a superior biomarker. AT1-AA may represent a better marker for late disease, whereas sFlt1 is a better marker for early onset disease.
    Type of Medium: Online Resource
    ISSN: 0194-911X , 1524-4563
    URL: Article
    DOI: 10.1161/HYPERTENSIONAHA.108.124115
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2009
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  • 6
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    Immunology in Hypertension, Preeclampsia, and Target-Organ Damage
    Ovid Technologies (Wolters Kluwer Health) ; 2009
    In:  Hypertension Vol. 54, No. 3 ( 2009-09), p. 439-443
    Details
    In: Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 54, No. 3 ( 2009-09), p. 439-443
    Type of Medium: Online Resource
    ISSN: 0194-911X , 1524-4563
    URL: Article
    DOI: 10.1161/HYPERTENSIONAHA.108.120253
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2009
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  • 7
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    Effects of Circulating and Local Uteroplacental Angiotensin II in Rat Pregnancy
    Ovid Technologies (Wolters Kluwer Health) ; 2010
    In:  Hypertension Vol. 56, No. 2 ( 2010-08), p. 311-318
    Details
    In: Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 56, No. 2 ( 2010-08), p. 311-318
    Abstract: The renin-angiotensin (Ang) system is important during placental development. Dysregulation of the renin-Ang system is important in preeclampsia (PE). Female rats transgenic for the human angiotensinogen gene crossed with males transgenic for the human renin gene develop the PE syndrome, whereas those of the opposite cross do not. We used this model to study the role of Ang II in trophoblast invasion, which is shallow in human PE but deeper in this model. We investigated the following groups: PE rats, opposite-cross rats, Ang II–infused rats (1000 ng/kg per day), and control rats. Ang II infusion increased only circulating Ang II levels (267.82 pg/mL), opposite cross influenced only uteroplacental Ang II (13.52 fmol/mg of protein), and PE increased both circulating (251.09 pg/mL) and uteroplacental (19.24 fmol/mg of protein) Ang II. Blood pressure and albuminuria occurred in the models with high circulating Ang II but not in the other models. Trophoblast invasion increased in PE and opposite-cross rats but not in Ang II–infused rats. Correspondingly, uterine artery resistance index increased in Ang II–infused rats but decreased in PE rats. We then studied human trophoblasts and villous explants from first-trimester pregnancies with time-lapse microscopy. Local Ang II dose-dependently increased migration by 75%, invasion by 58%, and motility by 282%. The data suggest that local tissue Ang II stimulates trophoblast invasion in vivo in the rat and in vitro in human cells, a hitherto fore unrecognized function. Conceivably, upregulation of tissue Ang II in the maternal part of the placenta represents an important growth factor for trophoblast invasion and migration.
    Type of Medium: Online Resource
    ISSN: 0194-911X , 1524-4563
    URL: Article
    DOI: 10.1161/HYPERTENSIONAHA.110.150961
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2010
    detail.hit.zdb_id: 2094210-2
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  • 8
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    Online Resource
    Angiogenic Factors and the Risk of Adverse Outcomes in Women With Suspected Preeclampsia
    Ovid Technologies (Wolters Kluwer Health) ; 2012
    In:  Circulation Vol. 125, No. 7 ( 2012-02-21), p. 911-919
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 125, No. 7 ( 2012-02-21), p. 911-919
    Abstract: An imbalance in circulating angiogenic factors plays a central role in the pathogenesis of preeclampsia. Methods and Results— We prospectively studied 616 women who were evaluated for suspected preeclampsia. We measured plasma levels of antiangiogenic soluble fms-like tyrosine kinase 1 (sFlt1) and proangiogenic placental growth factor (PlGF) at presentation and examined for an association between the sFlt1/PlGF ratio and subsequent adverse maternal and perinatal outcomes within 2 weeks. The median sFlt1/PlGF ratio at presentation was elevated in participants who experienced any adverse outcome compared with those who did not (47.0 [25th–75th percentile, 15.5–112.2] versus 10.8 [25th–75th percentile, 4.1–28.6] ; P 〈 0.0001). Among those presenting at 〈 34 weeks (n=167), the results were more striking (226.6 [25th–75th percentile, 50.4–547.3] versus 4.5 [25th–75th percentile, 2.0–13.5] ; P 〈 0.0001), and the risk was markedly elevated when the highest sFlt1/PlGF ratio tertile was compared with the lowest (odds ratio, 47.8; 95% confidence interval, 14.6–156.6). Among participants presenting at 〈 34 weeks, the addition of sFlt1/PlGF ratio to hypertension and proteinuria significantly improved the prediction for subsequent adverse outcomes (area under the curve, 0.93 for hypertension, proteinuria, and sFlt1/PlGF versus 0.84 for hypertension and proteinuria alone; P =0.001). Delivery occurred within 2 weeks of presentation in 86.0% of women with an sFlt1/PlGF ratio ≥85 compared with 15.8% of women with an sFlt1/PlGF ratio 〈 85 (hazard ratio, 15.2; 95% confidence interval, 8.0–28.7). Conclusions— In women with suspected preeclampsia presenting at 〈 34 weeks, circulating sFlt1/PlGF ratio predicts adverse outcomes occurring within 2 weeks. The accuracy of this test is substantially better than that of current approaches and may be useful in risk stratification and management. Additional studies are warranted to validate these findings.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/CIRCULATIONAHA.111.054361
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2012
    detail.hit.zdb_id: 1466401-X
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  • 9
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    European Association of Perinatal Medicine (EAPM), European Board and College of Obstetricians and Gynaecologists (EBCOG), European Midwives Association (EMA). Joint position statement: Substandard and disrespectful care in labour – because words matter
    Elsevier BV ; 2024
    In:  European Journal of Obstetrics & Gynecology and Reproductive Biology Vol. 296 ( 2024-05), p. 205-207
    Details
    In: European Journal of Obstetrics & Gynecology and Reproductive Biology, Elsevier BV, Vol. 296 ( 2024-05), p. 205-207
    Type of Medium: Online Resource
    ISSN: 0301-2115
    URL: Article
    DOI: 10.1016/j.ejogrb.2024.02.048
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2024
    detail.hit.zdb_id: 2005196-7
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  • 10
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    Allgemeine Gynäkologie / Prävention – Was gibt es Neues zur Vorhersage der Präeklampsie?
    Georg Thieme Verlag KG ; 2016
    In:  Geburtshilfe und Frauenheilkunde Vol. 76, No. 11 ( 2016-11-25), p. 1121-1122
    Details
    In: Geburtshilfe und Frauenheilkunde, Georg Thieme Verlag KG, Vol. 76, No. 11 ( 2016-11-25), p. 1121-1122
    Type of Medium: Online Resource
    ISSN: 0016-5751 , 1438-8804
    URL: Article
    DOI: 10.1055/s-0042-114861
    Language: German
    Publisher: Georg Thieme Verlag KG
    Publication Date: 2016
    detail.hit.zdb_id: 2026496-3
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