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Biomedicines
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The Pathophysiology of Preeclampsia
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The Pathophysiology of Preeclampsia

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular and Translational Medicine".

Deadline for manuscript submissions: closed (31 January 2024) | Viewed by 8202

Special Issue Editor

Prof. Dr. Marzena Laskowska

E-Mail Website
Guest Editor
Department of Obstetrics and Perinatology, Medical University of Lublin, Lublin, Poland
Interests: preeclampsia; maternal-fetal and neonatal medicine; HELLP; placenta; fetal growth restriction (FGR)
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Preeclampsia is a multisystem, specific for human pregnancy, disease,  and is a cause of serious complications for both the pregnant woman and her baby. Preeclampsia may lead to foetal growth restriction (FGR), premature birth, or intrauterine foetal death. In severe cases, an attack of eclamptic seizures, premature separation of the placenta, DIC, intracranial haemorrhage, HELLP syndrome, renal failure, and even maternal and foetal death may occur.

The current approved anti-hypertensive therapies have no effect on the progression of preeclampsia. The only known causal treatment is delivery. Although we currently know several pathogenetic mechanisms that may lead to the development of preeclampsia but its precise aetiopathogenesis is still unclear. Numerous attempts are still being made to search for the factor or factors responsible for the development of the disease.

The advancement of knowledge about the aetiology and pathomechanism responsible for disorders in preeclampsia may allow the implementation of appropriate prophylaxis and optimal treatment in a woman with preeclampsia, which will contribute to the improvement of perinatal outcomes and reducing maternal and neonatal mortality.

The aim of this Special Issue is to provide a review of aetiopathogenesis of preeclampsia. Laboratory and clinical researchers are welcomed to submit their works that contribute to better pregnancy outcomes in preeclamptic women. Thus, all original research articles or reviews on topics related to pregnancy in women with preeclampsia and HELLP syndrome are welcome in this Special Issue. Topics will include:

  • Preeclampsia and hypertension in pregnant women—aetiopathogenesis, pathophysiology, causes, complications;
  • HELLP syndrome—diagnosis, pathophysiology;
  • Placenta in preeclampsia—what has gone wrong;
  • Foetal complications.

Prof. Dr. Marzena Laskowska
Guest Editor

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Keywords

  • preeclampsia
  • eclamptic convulsions
  • HELLP
  • placenta
  • foetal growth restriction (FGR)
  • complications
  • pathophysiology
  • aetiopathogenesis

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Published Papers (4 papers)

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Research

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15 pages, 1399 KiB  
Article
Longitudinal 8-Epi-Prostaglandin F2-Alpha and Angiogenic Profile Mediator Evaluation during Pregnancy in Women with Suspected or Confirmed Pre-eclampsia
by Anda Lorena Dijmărescu, Florentina Tănase, Marius Bogdan Novac, Mirela Anişoara Siminel, Ionela Rotaru, Daniel Cosmin Caragea, Maria Magdalena Manolea, Constantin-Cristian Văduva, Mihail Virgil Boldeanu and Lidia Boldeanu
Biomedicines 2024, 12(2), 433; https://doi.org/10.3390/biomedicines12020433 - 14 Feb 2024
Cited by 1 | Viewed by 1356
Abstract
Background: In this exploratory study, we aimed to evaluate the dynamics of angiogenic [soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF), soluble Endoglin (sEng), and sFlt-1/PlGF, PlGF/sFlt-1, and sEng/PlGF ratios] and oxidative stress [8-epi-prostaglandin F2 alpha (8-epi-PGF2α) and 8-epi-PGF2α/PlGF ratio] mediator [...] Read more.
Background: In this exploratory study, we aimed to evaluate the dynamics of angiogenic [soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF), soluble Endoglin (sEng), and sFlt-1/PlGF, PlGF/sFlt-1, and sEng/PlGF ratios] and oxidative stress [8-epi-prostaglandin F2 alpha (8-epi-PGF2α) and 8-epi-PGF2α/PlGF ratio] mediator levels in women with suspected or confirmed pre-eclampsia (PE) at least two times during pregnancy. We also wanted to identify the possible correlations between 8-epi-PGF2α and angiogenic mediator levels at the time of inclusion of pregnant women. Methods: We included 40 pregnant women with suspected or confirmed PE, with a mean age of 29 years (range between 18 and 41 years) and gestational age between 18 and 28 weeks at inclusion in this study. The Enzyme-Linked Immunosorbent Assay (ELISA) method to measure the levels of serum angiogenic and oxidative stress mediators was used. Results: The evaluation of baseline sFlt-1/PlGF ratios using a cut-off of 38 suggested that 25 pregnant women had a sFlt-1/PlGF ratio of >38 (sFlt-1/PlGF ratio of >38 group) and 15 had a sFlt-1/PlGF ratio of ≤38 (sFlt-1/PlGF ratio of ≤38 group). The increases in sFlt-1/PlGF ratio in the sFlt-1/PlGF ratio of >38 group were caused by both an increase in sFlt-1 (2.04-fold) and a decrease in PlGF levels (2.55-fold). The 8-epi-PGF2α median levels were higher in the sFlt-1/PlGF ratio of >38 group (1.62-fold). During follow-up after pregnancy, we observed that the mean values of sFlt-1 and sEng and the median values of 8-epi-PGF2α and sFlt-1/PlGF, sEng/PlGF, and 8-epi-PGF2α/PlGF ratios increased directly proportional to gestational age for each measurement time until delivery in both groups. For five women who had a sFlt-1/PlGF ratio ≤38 at inclusion, sFlt-1/PlGF ratio was observed to increase to >38 later in pregnancy. We observed that, in the sFlt-1/PlGF ratio >38 group, baseline 8-epi-PGF2α levels better correlated with angiogenic mediator levels. Conclusions: Our study shows that 33.33% of pregnant women evaluated for suspected or confirmed PE with a sFlt-1/PlGF ratio of ≤38 displayed a rise in sFlt-1/PlGF ratio in subsequent weeks. In addition, together with angiogenic mediators, 8-epi-PGF2 α can be utilized as an independent predictor factor to help clinicians identify or predict which pregnant women will develop PE. Full article
(This article belongs to the Special Issue The Pathophysiology of Preeclampsia)
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11 pages, 1048 KiB  
Article
Impact of Angiogenic and Cardiovascular Biomarkers for Prediction of Placental Dysfunction in the First Trimester of Pregnancy
by Madalina Nicoleta Nan, Álvaro García-Osuna, Josefina Mora, Cristina Trilla, Assumpta Antonijuan, Vanesa Orantes, Mónica Cruz-Lemini, Francisco Blanco-Vaca and Elisa Llurba
Biomedicines 2023, 11(5), 1327; https://doi.org/10.3390/biomedicines11051327 - 29 Apr 2023
Viewed by 2008
Abstract
Algorithms for first-trimester prediction of pre-eclampsia usually include maternal risk factors, blood pressure, placental growth factor (PlGF), and uterine artery Doppler pulsatility index. However, these models lack sensitivity for the prediction of late-onset pre-eclampsia and other placental complications of pregnancy, such as small [...] Read more.
Algorithms for first-trimester prediction of pre-eclampsia usually include maternal risk factors, blood pressure, placental growth factor (PlGF), and uterine artery Doppler pulsatility index. However, these models lack sensitivity for the prediction of late-onset pre-eclampsia and other placental complications of pregnancy, such as small for gestational age infants or preterm birth. The aim of this study was to assess the screening performance of PlGF, soluble fms-like tyrosine kinase-1 (sFlt-1), N-terminal pro-brain natriuretic peptide (NT-proBNP), uric acid, and high-sensitivity cardiac troponin T (hs-TnT) in the prediction of adverse obstetric outcomes related to placental insufficiency. This retrospective case–control study was based on a cohort of 1390 pregnant women, among which 210 presented pre-eclampsia, small for gestational age infants, or preterm birth. Two hundred and eight women with healthy pregnancies were selected as controls. Serum samples were collected between weeks 9 and 13 of gestation, and maternal serum concentrations of PlGF, sFlt-1, NT-proBNP, uric acid, and hs-TnT were measured. Multivariate regression analysis was used to generate predictive models combining maternal factors with the above-mentioned biomarkers. Women with placental dysfunction had lower median concentrations of PlGF (25.77 vs. 32.00 pg/mL; p < 0.001), sFlt-1 (1212.0 vs. 1363.5 pg/mL; p = 0.001), and NT-proBNP (51.22 vs. 68.71 ng/L; p < 0.001) and higher levels of uric acid (193.66 µmol/L vs. 177.40 µmol/L; p = 0.001). There was no significant difference between groups regarding the sFlt-1/PlGF ratio. Hs-TnT was not detected in 70% of the maternal serums analyzed. Altered biomarker concentrations increased the risk of the analyzed complications both in univariate and multivariate analyses. The addition of PlGF, sFlt-1, and NT-proBNP to maternal variables improved the prediction of pre-eclampsia, small for gestational age infants, and preterm birth (area under the curve: 0.710, 0.697, 0.727, and 0.697 vs. 0.668, respectively). Reclassification improvement was greater in maternal factors plus the PlGF model and maternal factors plus the NT-p roBNP model (net reclassification index, NRI: 42.2% and 53.5%, respectively). PlGF, sFlt-1, NT-proBNP, and uric acid measurements in the first trimester of pregnancy, combined with maternal factors, can improve the prediction of adverse perinatal outcomes related to placental dysfunction. In addition to PlGF, uric acid and NT-proBNP are two promising predictive biomarkers for placental dysfunction in the first trimester of pregnancy. Full article
(This article belongs to the Special Issue The Pathophysiology of Preeclampsia)
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12 pages, 805 KiB  
Article
Preeclampsia Susceptibility Assessment Based on Deep Learning Modeling and Single Nucleotide Polymorphism Analysis
by Aida Saadaty, Sara Parhoudeh, Khalil Khashei Varnamkhasti, Mehdi Moghanibashi and Sirous Naeimi
Biomedicines 2023, 11(5), 1257; https://doi.org/10.3390/biomedicines11051257 - 24 Apr 2023
Viewed by 2013
Abstract
The early diagnosis of preeclampsia, a key outlook in improving pregnancy outcomes, still remains elusive. The present study aimed to examine the interleukin-13 and interleukin-4 pathway potential in the early detection of preeclampsia as well as the relationship between interleukin-13 rs2069740(T/A) and rs34255686(C/A) [...] Read more.
The early diagnosis of preeclampsia, a key outlook in improving pregnancy outcomes, still remains elusive. The present study aimed to examine the interleukin-13 and interleukin-4 pathway potential in the early detection of preeclampsia as well as the relationship between interleukin-13 rs2069740(T/A) and rs34255686(C/A) polymorphisms and preeclampsia risk to present a combined model. This study utilized raw data from the GSE149440 microarray dataset, and an expression matrix was constructed using the RMA method and affy package. The genes related to the interleukin-13 and interleukin-4 pathway were extracted from the GSEA, and their expression levels were applied to design multilayer perceptron and PPI graph convolutional neural network models. Moreover, genotyping for the rs2069740(T/A) and rs34255686(C/A) polymorphisms of the interleukin-13 gene were tested using the amplification refractory mutation system PCR method. The outcomes revealed that the expression levels of interleukin-4 and interleukin-13 pathway genes could significantly differentiate early preeclampsia from normal pregnancy. Moreover, the present study’s data suggested significant differences in the genotype distribution, the allelic frequencies and some of the risk markers of the study, in the position of rs34255686 and rs2069740 polymorphisms between the case and control groups. A combined test of two single nucleotide polymorphisms and an expression-based deep learning model could be designed for future preeclampsia diagnostic purposes. Full article
(This article belongs to the Special Issue The Pathophysiology of Preeclampsia)
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Review

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13 pages, 1088 KiB  
Review
Tissue Factor Pathway Inhibitors as Potential Targets for Understanding the Pathophysiology of Preeclampsia
by Hiroshi Kobayashi, Sho Matsubara, Chiharu Yoshimoto, Hiroshi Shigetomi and Shogo Imanaka
Biomedicines 2023, 11(5), 1237; https://doi.org/10.3390/biomedicines11051237 - 22 Apr 2023
Cited by 4 | Viewed by 2030
Abstract
Background: Preeclampsia is a hypertensive disorder of pregnancy that causes maternal and perinatal morbidity and mortality worldwide. Preeclampsia is associated with complex abnormalities of the coagulation and fibrinolytic system. Tissue factor (TF) is involved in the hemostatic system during pregnancy, while the Tissue [...] Read more.
Background: Preeclampsia is a hypertensive disorder of pregnancy that causes maternal and perinatal morbidity and mortality worldwide. Preeclampsia is associated with complex abnormalities of the coagulation and fibrinolytic system. Tissue factor (TF) is involved in the hemostatic system during pregnancy, while the Tissue Factor Pathway Inhibitor (TFPI) is a major physiological inhibitor of the TF-initiated coagulation cascade. The imbalance in hemostatic mechanisms may lead to a hypercoagulable state, but prior research has not comprehensively investigated the roles of TFPI1 and TFPI2 in preeclamptic patients. In this review, we summarize our current understanding of the biological functions of TFPI1 and TFPI2 and discuss future directions in preeclampsia research. Methods: A literature search was performed from inception to 30 June 2022 in the PubMed and Google Scholar databases. Results: TFPI1 and TFPI2 are homologues with different protease inhibitory activities in the coagulation and fibrinolysis system. TFPI1 is an essential physiological inhibitor of the TF-initiated extrinsic pathway of coagulation. On the other hand, TFPI2 inhibits plasmin-mediated fibrinolysis and exerts antifibrinolytic activity. It also inhibits plasmin-mediated inactivation of clotting factors and maintains a hypercoagulable state. Furthermore, in contrast to TFPI1, TFPI2 suppresses trophoblast cell proliferation and invasion and promotes cell apoptosis. TFPI1 and TFPI2 may play important roles in regulating the coagulation and fibrinolytic system and trophoblast invasion to establish and maintain successful pregnancies. Concentrations of TF, TFPI1, and TFPI2 in maternal blood and placental tissue are significantly altered in preeclamptic women compared to normal pregnancies. Conclusions: TFPI protein family may affect both the anticoagulant (i.e., TFPI1) and antifibrinolytic/procoagulant (i.e., TFPI2) systems. TFPI1 and TFPI2 may function as new predictive biomarkers for preeclampsia and navigate precision therapy. Full article
(This article belongs to the Special Issue The Pathophysiology of Preeclampsia)
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