Submit to Special Issue Submit Abstract to Special Issue Review for IJMS Propose a Special Issue

Journal Menu

Journal Browser

Recent Molecular Research on Preeclampsia

Print Special Issue Flyer
Special Issue Editors
Special Issue Information
Keywords
Published Papers

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 15 May 2024 | Viewed by 11895

Share This Special Issue

Special Issue Editor

Dr. Natalia I. Agalakova

E-Mail Website
Guest Editor

Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, 191186 St. Petersburg, Russia
Interests: marinobufagenin; ouabain; adenosine triphosphatase (potassium sodium) fluorosis; sodium fluorides; sickle cell anemia; potassium-chloride symporters
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Preeclampsia (PE) is a serious hypertensive complication of pregnancy associated with a high rate of maternal and perinatal morbidity and mortality. Despite a search for therapy, PE still lacks effective treatment other than delivery. Recent works have revealed a multitude of pathophysiological mechanisms implicated in the development of this disorder, including general endothelial dysfunction, placental abnormalities, aberrant production of angiogenic factors, vasoactive substances, placental steroid and peptide hormones, oxidative stress, as well as heritable and inflammatory components. However, in spite of these efforts, the etiology of PE remains elusive, while therapeutic targets are not identified. A better knowledge of the underlying molecular mechanisms and genetic landscape of PE is urgently needed to understand the PE pathogenesis and development of specific and innovative therapies.

This Special Issue will include the original articles and reviews that focus on the most advanced knowledge of molecular mechanisms responsible for the onset and progression of PE, including the contribution of genetic and epigenetic factors, oxidative and inflammatory imbalance, as well as the possible link between PE and pathological processes in the brain. Interdisciplinary approaches aiming to shed light on the complex machinery of PE are warmly invited. The manuscripts revealing the molecular targets which can open new routes for the development of novel potential preventive and therapeutic strategies are also welcome.

Dr. Natalia I. Agalakova
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

preeclampsia
molecular signaling
transcription factors
translational regulation
genetic predisposition
epigenetic regulation
angiogenic markers
inflammation markers
metabolomics
transcriptomics

Published Papers (11 papers)

Download All Papers

Research

Jump to: Review

20 pages, 3228 KiB

Open AccessArticle

Assessment of Red Blood Cell Aggregation in Preeclampsia by Microfluidic Image Flow Analysis—Impact of Oxidative Stress on Disease Severity

by Anika Alexandrova-Watanabe, Emilia Abadjieva, Ina Giosheva, Ariana Langari, Tihomir Tiankov, Emil Gartchev, Regina Komsa-Penkova and Svetla Todinova

Int. J. Mol. Sci. 2024, 25(7), 3732; https://doi.org/10.3390/ijms25073732 - 27 Mar 2024

Viewed by 602

Abstract

Preeclampsia (PE) is a hypertensive disease characterized by proteinuria, endothelial dysfunction, and placental hypoxia. Reduced placental blood flow causes changes in red blood cell (RBC) rheological characteristics. Herein, we used microfluidics techniques and new image flow analysis to evaluate RBC aggregation in preeclamptic and normotensive pregnant women. The results demonstrate that RBC aggregation depends on the disease severity and was higher in patients with preterm birth and low birth weight. The RBC aggregation indices (EAI) at low shear rates were higher for non-severe (0.107 ± 0.01) and severe PE (0.149 ± 0.05) versus controls (0.085 ± 0.01; p < 0.05). The significantly more undispersed RBC aggregates were found at high shear rates for non-severe (18.1 ± 5.5) and severe PE (25.7 ± 5.8) versus controls (14.4 ± 4.1; p < 0.05). The model experiment with in-vitro-induced oxidative stress in RBCs demonstrated that the elevated aggregation in PE RBCs can be partially due to the effect of oxidation. The results revealed that RBCs from PE patients become significantly more adhesive, forming large, branched aggregates at a low shear rate. Significantly more undispersed RBC aggregates at high shear rates indicate the formation of stable RBC clusters, drastically more pronounced in patients with severe PE. Our findings demonstrate that altered RBC aggregation contributes to preeclampsia severity. Full article

(This article belongs to the Special Issue Recent Molecular Research on Preeclampsia)

► Show Figures

Figure 1

27 pages, 3510 KiB

Open AccessArticle

Maternal Age at Menarche Genes Determines Fetal Growth Restriction Risk

by Evgeny Reshetnikov, Maria Churnosova, Yuliya Reshetnikova, Vadim Stepanov, Anna Bocharova, Victoria Serebrova, Ekaterina Trifonova, Irina Ponomarenko, Inna Sorokina, Olga Efremova, Valentina Orlova, Irina Batlutskaya, Marina Ponomarenko, Vladimir Churnosov, Inna Aristova, Alexey Polonikov and Mikhail Churnosov

Int. J. Mol. Sci. 2024, 25(5), 2647; https://doi.org/10.3390/ijms25052647 - 24 Feb 2024

Cited by 1 | Viewed by 559

Abstract

We aimed to explore the potential link of maternal age at menarche (mAAM) gene polymorphisms with risk of the fetal growth restriction (FGR). This case (FGR)–control (FGR free) study included 904 women (273 FGR and 631 control) in the third trimester of gestation examined/treated in the Departments of Obstetrics. For single nucleotide polymorphism (SNP) multiplex genotyping, 50 candidate loci of mAAM were chosen. The relationship of mAAM SNPs and FGR was appreciated by regression procedures (logistic/model-based multifactor dimensionality reduction [MB-MDR]) with subsequent in silico assessment of the assumed functionality pithy of FGR-related loci. Three mAAM-appertain loci were FGR-linked to genes such as KISS1 (rs7538038) (effect allele G-odds ratio (OR)_allelic = 0.63/p_perm = 0.0003; OR_additive = 0.61/p_perm = 0.001; OR_dominant = 0.56/p_perm = 0.001), NKX2-1 (rs999460) (effect allele A-OR_allelic = 1.37/p_perm = 0.003; OR_additive = 1.45/p_perm = 0.002; OR_recessive = 2.41/p_perm = 0.0002), GPRC5B (rs12444979) (effect allele T-OR_allelic = 1.67/p_perm = 0.0003; OR_dominant = 1.59/p_perm = 0.011; OR_additive = 1.56/p_perm = 0.009). The haplotype ACA FSHB gene (rs555621*rs11031010*rs1782507) was FRG-correlated (OR = 0.71/p_perm = 0.05). Ten FGR-implicated interworking models were founded for 13 SNPs (p_perm ≤ 0.001). The rs999460 NKX2-1 and rs12444979 GPRC5B interplays significantly influenced the FGR risk (these SNPs were present in 50% of models). FGR-related mAAM-appertain 15 polymorphic variants and 350 linked SNPs were functionally momentous in relation to 39 genes participating in the regulation of hormone levels, the ovulation cycle process, male gonad development and vitamin D metabolism. Thus, this study showed, for the first time, that the mAAM-appertain genes determine FGR risk. Full article

(This article belongs to the Special Issue Recent Molecular Research on Preeclampsia)

► Show Figures

Figure 1

12 pages, 832 KiB

Open AccessCommunication

Inhibition of Caspase 1 Reduces Blood Pressure, Cytotoxic NK Cells, and Inflammatory T-Helper 17 Cells in Placental Ischemic Rats

by Corbin A. Shields, Geilda A. Tardo, Xi Wang, Gregory Peacock, Marcus Robbins, Hannah Glenn, Rachel Wilson, Jan M. Williams and Denise C. Cornelius

Int. J. Mol. Sci. 2024, 25(2), 863; https://doi.org/10.3390/ijms25020863 - 10 Jan 2024

Viewed by 727

Abstract

Preeclampsia (PE) is characterized by maternal hypertension, fetal growth restriction (FGR), and increased inflammation and populations of cytotoxic NK cells (cNKs) and inflammatory T-Helper 17 cells (TH17s). Both cytotoxic NK cells and TH17 cells are heavily influenced via IL-1β signaling. Caspase 1 activity leads to the release of the inflammatory cytokine IL-1β, which is increased in women with PE. Therefore, we tested the hypothesis that the inhibition of Caspase 1 with VX-765 in rats with reduced uterine perfusion pressure (RUPP) will attenuate PE pathophysiology. On gestation day (GD) 14, timed pregnant Sprague–Dawley rats underwent the RUPP or Sham procedure and were separated into groups that received either vehicle or VX-765 (50 mg/kg/day i.p.). On GD19, MAP was measured via carotid catheter and blood and tissues were collected. Bio-Plex and flow cytometry analysis were performed on placental tissues. Placental IL-1β was increased in the RUPP rats vs. the Sham rats and treatment with VX-765 reduced IL-1β in the RUPP rats. Caspase 1 inhibition reduced placental cNKs and TH17s in RUPP rats compared to vehicle-treated RUPP rats. Increased MAP was observed in RUPP rats compared with Sham rats and was reduced in RUPP + VX-765 rats. Placental reactive oxygen species (ROS) were elevated in RUPP rats compared to Sham rats. VX-765 administration reduced ROS in treated RUPP rats. Caspase 1 inhibition increased the number of live pups, yet had no effect on fetal weight or placental efficiency in the treated groups. In conclusion, Caspase 1 inhibition reduces placental IL-1β, inflammatory TH17 and cNK populations, and reduces MAP in RUPP rats. These data suggest that Caspase 1 is a key contributor to PE pathophysiology. This warrants further investigation of Caspase 1 as a potential therapeutic target to improve maternal outcomes in PE. Full article

(This article belongs to the Special Issue Recent Molecular Research on Preeclampsia)

► Show Figures

Figure 1

12 pages, 2320 KiB

Open AccessArticle

Regulation of MMP-2 by IL-8 in Vascular Endothelial Cells: Probable Mechanism for Endothelial Dysfunction in Women with Preeclampsia

by Arturo Flores-Pliego, Aurora Espejel-Nuñez, Hector Borboa-Olivares, Sandra Berenice Parra-Hernández, Araceli Montoya-Estrada, Humberto González-Márquez, Ramón González-Camarena and Guadalupe Estrada-Gutierrez

Int. J. Mol. Sci. 2024, 25(1), 122; https://doi.org/10.3390/ijms25010122 (registering DOI) - 21 Dec 2023

Viewed by 606

Abstract

Endothelial dysfunction (ED) in preeclampsia (PE) results from the convergence of oxidative stress, inflammation, and alterations in extracellular matrix components, affecting vascular tone and permeability. The molecular network leading to ED includes IL-8 and MMP-2. In vitro, IL-8 regulates the concentration and activity of MMP-2 in the trophoblast; this interaction has not been studied in endothelial cells during PE. We isolated human umbilical vein endothelial cells (HUVECs) from women with healthy pregnancies (NP, n = 15) and PE (n = 15). We quantified the intracellular concentration of nitric oxide and reactive oxygen species with colorimetric assays, IL-8 with ELISA, and MMP-2 with zymography and using an ELISA-type system. An IL-8 inhibition assay was used to study the influence of this cytokine on MMP-2 concentration and activity. HUVECs from women with PE showed significantly higher oxidative stress than NP. IL-8 and MMP-2 were found to be significantly elevated in PE HUVECs compared to NP. Inhibition of IL-8 in HUVECs from women with PE significantly decreased the concentration of MMP-2. We demonstrate that IL-8 is involved in the mechanisms of MMP-2 expression in HUVECs from women with PE. Our findings provide new insights into the molecular mechanisms regulating the ED distinctive of PE. Full article

(This article belongs to the Special Issue Recent Molecular Research on Preeclampsia)

► Show Figures

Figure 1

21 pages, 2143 KiB

Open AccessArticle

Quantitative Proteomics of Maternal Blood Plasma in Isolated Intrauterine Growth Restriction

by Natalia L. Starodubtseva, Alisa O. Tokareva, Maria V. Volochaeva, Alexey S. Kononikhin, Alexander G. Brzhozovskiy, Anna E. Bugrova, Angelika V. Timofeeva, Evgenii N. Kukaev, Victor L. Tyutyunnik, Natalia E. Kan, Vladimir E. Frankevich, Evgeny N. Nikolaev and Gennady T. Sukhikh

Int. J. Mol. Sci. 2023, 24(23), 16832; https://doi.org/10.3390/ijms242316832 - 27 Nov 2023

Viewed by 1121

Abstract

Intrauterine growth restriction (IUGR) remains a significant concern in modern obstetrics, linked to high neonatal health problems and even death, as well as childhood disability, affecting adult quality of life. The role of maternal and fetus adaptation during adverse pregnancy is still not completely understood. This study aimed to investigate the disturbance in biological processes associated with isolated IUGR via blood plasma proteomics. The levels of 125 maternal plasma proteins were quantified by liquid chromatography-multiple reaction monitoring mass spectrometry (LC-MRM MS) with corresponding stable isotope-labeled peptide standards (SIS). Thirteen potential markers of IUGR (Gelsolin, Alpha-2-macroglobulin, Apolipoprotein A-IV, Apolipoprotein B-100, Apolipoprotein(a), Adiponectin, Complement C5, Apolipoprotein D, Alpha-1B-glycoprotein, Serum albumin, Fibronectin, Glutathione peroxidase 3, Lipopolysaccharide-binding protein) were found to be inter-connected in a protein–protein network. These proteins are involved in plasma lipoprotein assembly, remodeling, and clearance; lipid metabolism, especially cholesterol and phospholipids; hemostasis, including platelet degranulation; and immune system regulation. Additionally, 18 proteins were specific to a particular type of IUGR (early or late). Distinct patterns in the coagulation and fibrinolysis systems were observed between isolated early- and late-onset IUGR. Our findings highlight the complex interplay of immune and coagulation factors in IUGR and the differences between early- and late-onset IUGR and other placenta-related conditions like PE. Understanding these mechanisms is crucial for developing targeted interventions and improving outcomes for pregnancies affected by IUGR. Full article

(This article belongs to the Special Issue Recent Molecular Research on Preeclampsia)

► Show Figures

Figure 1

16 pages, 1623 KiB

Open AccessArticle

Exploring the Potential of Olfactory Receptor Circulating RNA Measurement for Preeclampsia Prediction and Its Linkage to Mild Gestational Hypothyroidism

by Andréa Harumy de Lima Hirata, Luiz Antônio de Jesus Rocha Camargo, Valdelena Alessandra da Silva, Robson José de Almeida, Lucas dos Santos Bacigalupo, Maria Clara Albejante, Flavia Salomão d’Avila Curi, Patrícia Varela, Leonardo Martins, João Bosco Pesquero, Humberto Delle and Cleber P. Camacho

Int. J. Mol. Sci. 2023, 24(23), 16681; https://doi.org/10.3390/ijms242316681 - 24 Nov 2023

Viewed by 1083

Abstract

Gestational hypothyroidism may lead to preeclampsia development. However, this pathophysiological is unknown. We expect to find a shared mechanism by comparing hypothyroidism and preeclampsia. From our transcriptome data, we recognized olfactory receptors as that fingerprint. The reduction of taste and smell in hypothyroid patients has been known for a long time. Therefore, we decided to look to the olfactory receptors and aimed to identify genes capable of predicting preeclampsia (PEC). Methods: An Ion Proton Sequencer (Thermo Fisher Scientific, Waltham, MA, USA) was used to construct the transcriptome databases. RStudio with packages Limma v.3.50.0, GEOquery v.2.62.2, and umap v.0.2.8.8 were used to analyze the differentially expressed genes in GSE149440 from the Gene Expression Omnibus (GEO). The 7500 Real-Time PCR System (Applied Biosystems, Foster City, CA, USA) was used for RT-qPCR amplification of OR6X1 and OR4E2. Results: Our transcriptomic datasets analysis revealed 25.08% and 26.75% downregulated olfactory receptor (ORs) in mild nontreated gestational hypothyroidism (GHT) and PEC, respectively. In the GSE149440 GEO dataset, we found OR5H1, OR5T3, OR51A7, OR51B6, OR10J5, OR6C6, and OR2AG2 as predictors of early-onset PEC. We also evaluate two chosen biomarkers’ responses to levothyroxine. The RT-qPCR demonstrated a difference in OR6X1 and OR4E2 expression between GHT and healthy pregnancy (p < 0.05). Those genes presented a negative correlation with TSH (r: −0.51, p < 0.05; and r: −0.44, p < 0.05), a strong positive correlation with each other (r: 0.89; p < 0.01) and the levothyroxine-treated group had no difference from the healthy one. We conclude that ORs could be used as biomarkers at the beginning of gestation, and the downregulated ORs found in GHT may be improved with levothyroxine treatment. Full article

(This article belongs to the Special Issue Recent Molecular Research on Preeclampsia)

► Show Figures

Figure 1

14 pages, 6235 KiB

Open AccessArticle

APOA1 Is a Novel Marker for Preeclampsia

by Zhenzhen Liu, Jiangnan Pei, Xiaoyue Zhang, Chengjie Wang, Yao Tang, Haiyan Liu, Yi Yu, Shouling Luo and Weirong Gu

Int. J. Mol. Sci. 2023, 24(22), 16363; https://doi.org/10.3390/ijms242216363 - 15 Nov 2023

Cited by 1 | Viewed by 921

Abstract

Preeclampsia (PE) is one of the pregnancy complications, leading to major maternal and fetal morbidity and mortality; however, the underlying mechanisms of PE still remain unclear. We aimed to explore the role of apolipoprotein A1 (APOA1) in the pathophysiology of PE. The expression of APOA1 was elevated in both plasma and placental tissues, as detected by Western blotting, immunohistochemistry, and a qRT-PCR assay. Importantly, we detected the concentration of APOA1 using the ELISA assay in normal control women (n = 30) and women with preeclampsia (n = 29) from a prospective cohort study. The concentration of APOA1 was not significantly altered in plasma during early and mid-term gestation of the PE patients compared to the NP patients; however, it was elevated during late gestation. Additionally, the concentration of APOA1 was positively associated with systolic blood pressure during late gestation. The proliferation and invasion of trophoblast were all increased in HTR8/SVneo cells transfected with APOA1 siRNA and decreased in HTR8/SVneo cells treated with the recombinant human APOA1 protein (rhAPOA1). Additionally, we used public datasets to investigate the downstream genes of APOA1 and qRT-PCR for validation. Furthermore, we explored the transcriptional activity of peroxisome proliferator-activated receptor gamma (PPARγ) in APOA1 by using a luciferase assay, which showed that the APOA1 promoter was activated by PPARγ. Additionally, the inhibitory effect of rhAPOA1 on the ability of trophoblast invasion and proliferation can be rescued by the PPARγ inhibitor. Our findings suggest the crucial role of APOA1 in PE, which might provide a new strategy for the prevention and treatment of PE. Full article

(This article belongs to the Special Issue Recent Molecular Research on Preeclampsia)

► Show Figures

Figure 1

13 pages, 298 KiB

Open AccessArticle

Cholesterol Metabolic Profiling of HDL in Women with Late-Onset Preeclampsia

by Tamara Antonić, Daniela Ardalić, Sandra Vladimirov, Aleksandra Zeljković, Jelena Vekić, Marija Mitrović, Jasmina Ivanišević, Tamara Gojković, Jelena Munjas, Vesna Spasojević-Kalimanovska, Željko Miković and Aleksandra Stefanović

Int. J. Mol. Sci. 2023, 24(14), 11357; https://doi.org/10.3390/ijms241411357 - 12 Jul 2023

Cited by 1 | Viewed by 1196

Abstract

A specific feature of dyslipidemia in pregnancy is increased high-density lipoprotein (HDL) cholesterol concentration, which is probably associated with maternal endothelium protection. However, preeclampsia is most often associated with low HDL cholesterol, and the mechanisms behind this change are scarcely explored. We aimed to investigate changes in HDL metabolism in risky pregnancies and those complicated by late-onset preeclampsia. We analyze cholesterol synthesis (cholesterol precursors: desmosterol, 7-dehydrocholesterol, and lathosterol) and absorption markers (phytosterols: campesterol and β-sitosterol) within HDL particles (NCS_HDL), the activities of principal modulators of HDL cholesterol’s content, and major HDL functional proteins levels in mid and late pregnancy. On the basis of the pregnancy outcome, participants were classified into the risk group (RG) (70 women) and the preeclampsia group (PG) (20 women). HDL cholesterol was lower in PG in the second trimester compared to RG (p < 0.05) and followed by lower levels of cholesterol absorption markers (p < 0.001 for campesterol_HDL and p < 0.05 for β-sitosterol_HDL). Lowering of HDL cholesterol between trimesters in RG (p < 0.05) was accompanied by a decrease in HDL phytosterol content (p < 0.001), apolipoprotein A-I (apoA-I) concentration (p < 0.05), and paraoxonase 1 (PON1) (p < 0.001), lecithin–cholesterol acyltransferase (LCAT) (p < 0.05), and cholesterol ester transfer protein (CETP) activities (p < 0.05). These longitudinal changes were absent in PG. Development of late-onset preeclampsia is preceded by the appearance of lower HDL cholesterol and NCS_HDL in the second trimester. We propose that reduced capacity for intestinal HDL synthesis, decreased LCAT activity, and impaired capacity for HDL-mediated cholesterol efflux could be the contributing mechanisms resulting in lower HDL cholesterol. Full article

(This article belongs to the Special Issue Recent Molecular Research on Preeclampsia)

14 pages, 1373 KiB

Open AccessArticle

Investigating the Effects of Atrial Natriuretic Peptide on the Maternal Endothelium to Determine Potential Implications for Preeclampsia

by Natalie K. Binder, Sally Beard, Natasha de Alwis, Bianca R. Fato, Tuong-Vi Nguyen, Tu’uhevaha J. Kaitu’u-Lino and Natalie J. Hannan

Int. J. Mol. Sci. 2023, 24(7), 6182; https://doi.org/10.3390/ijms24076182 - 24 Mar 2023

Cited by 2 | Viewed by 1385

Abstract

Preeclampsia is associated with an increased lifelong risk of cardiovascular disease (CVD). It is not clear whether this is induced by persistent systemic organ and vascular damage following preeclampsia or due to a predisposition to both conditions that share cardiovascular pathophysiology. Common to both CVD and preeclampsia is the dysregulation of corin and its proteolytic product, atrial natriuretic peptide (ANP). ANP, a hypotensive hormone converted from pro-ANP by corin, is involved in blood pressure homeostasis. While corin is predominantly a cardiac enzyme, both corin and pro-ANP are significantly upregulated in the gravid uterus and dysregulated in preeclampsia. Relatively little is known about ANP function in the endothelium during a pregnancy complicated by preeclampsia. Here, we investigated the effect of ANP on endothelial cell proliferation and migration, markers of endothelial dysfunction, and receptor expression in omental arteries exposed to circulating preeclamptic toxins. ANP receptor expression is significantly upregulated in preeclamptic vasculature but not because of exposure to preeclampsia toxins tumour necrosis factor α or soluble fms-like tyrosine kinase-1. The supplementation of endothelial cells with ANP did not promote proliferation or migration, nor did ANP improve markers of endothelial dysfunction. The role of ANP in preeclampsia is unlikely to be via endothelial pathways. Full article

(This article belongs to the Special Issue Recent Molecular Research on Preeclampsia)

► Show Figures

Figure 1

Review

Jump to: Research

23 pages, 1897 KiB

Open AccessReview

The Pathophysiological, Genetic, and Hormonal Changes in Preeclampsia: A Systematic Review of the Molecular Mechanisms

by Yi-Ting Chiang, Kok-Min Seow and Kuo-Hu Chen

Int. J. Mol. Sci. 2024, 25(8), 4532; https://doi.org/10.3390/ijms25084532 - 20 Apr 2024

Viewed by 513

Abstract

Preeclampsia, a serious complication of pregnancy, involves intricate molecular and cellular mechanisms. Fetal microchimerism, where fetal cells persist within maternal tissues and in circulation, acts as a mechanistic link between placental dysfunction and maternal complications in the two-stage model of preeclampsia. Hormones, complements, and cytokines play pivotal roles in the pathophysiology, influencing immune responses, arterial remodeling, and endothelial function. Also, soluble HLA-G, involved in maternal–fetal immune tolerance, is reduced in preeclampsia. Hypoxia-inducible factor 1-alpha (Hif-α) dysregulation leads to placental abnormalities and preeclampsia-like symptoms. Alterations in matrix metalloproteinases (MMPs), endothelins (ETs), chemokines, and cytokines contribute to defective trophoblast invasion, endothelial dysfunction, and inflammation. Preeclampsia’s genetic complexity includes circRNAs, miRNAs, and lncRNAs. CircRNA_06354 is linked to early-onset preeclampsia by influencing trophoblast invasion via the hsa-miR-92a-3p/VEGF-A pathway. The dysregulation of C19MC, especially miR-519d and miR-517-5p, affects trophoblast function. Additionally, lncRNAs like IGFBP1 and EGFR-AS1, along with protein-coding genes, impact trophoblast regulation and angiogenesis, influencing both preeclampsia and fetal growth. Besides aberrations in CD31+ cells, other potential biomarkers such as MMPs, soluble HLA-G, and hCG hold promise for predicting preeclampsia and its complications. Therapeutic interventions targeting factors such as peroxisome PPAR-γ and endothelin receptors show potential in mitigating preeclampsia-related complications. In conclusion, preeclampsia is a complex disorder with a multifactorial etiology and pathogenesis. Fetal microchimerism, hormones, complements, and cytokines contribute to placental and endothelial dysfunction with inflammation. Identifying novel biomarkers and therapeutic targets offers promise for early diagnosis and effective management, ultimately reducing maternal and fetal morbidity and mortality. However, further research is warranted to translate these findings into clinical practice and enhance outcomes for at-risk women. Full article

(This article belongs to the Special Issue Recent Molecular Research on Preeclampsia)

► Show Figures

Figure 1

18 pages, 1057 KiB

Open AccessReview

Natriuretic Peptide Signaling in Uterine Biology and Preeclampsia

by Qingyu Wu

Int. J. Mol. Sci. 2023, 24(15), 12309; https://doi.org/10.3390/ijms241512309 - 01 Aug 2023

Cited by 1 | Viewed by 1668

Abstract

Endometrial decidualization is a uterine process essential for spiral artery remodeling, embryo implantation, and trophoblast invasion. Defects in endometrial decidualization and spiral artery remodeling are important contributing factors in preeclampsia, a major disorder in pregnancy. Atrial natriuretic peptide (ANP) is a cardiac hormone that regulates blood volume and pressure. ANP is also generated in non-cardiac tissues, such as the uterus and placenta. In recent human genome-wide association studies, multiple loci with genes involved in natriuretic peptide signaling are associated with gestational hypertension and preeclampsia. In cellular experiments and mouse models, uterine ANP has been shown to stimulate endometrial decidualization, increase TNF-related apoptosis-inducing ligand expression and secretion, and enhance apoptosis in arterial smooth muscle cells and endothelial cells. In placental trophoblasts, ANP stimulates adenosine 5′-monophosphate-activated protein kinase and the mammalian target of rapamycin complex 1 signaling, leading to autophagy inhibition and protein kinase N3 upregulation, thereby increasing trophoblast invasiveness. ANP deficiency impairs endometrial decidualization and spiral artery remodeling, causing a preeclampsia-like phenotype in mice. These findings indicate the importance of natriuretic peptide signaling in pregnancy. This review discusses the role of ANP in uterine biology and potential implications of impaired ANP signaling in preeclampsia. Full article

(This article belongs to the Special Issue Recent Molecular Research on Preeclampsia)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Recent Molecular Research on Preeclampsia

Share This Special Issue

Special Issue Editor

Special Issue Information

Keywords

Published Papers (11 papers)

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI