Preeclamptic Pregnancies Research Articles

Transcriptomic profiling with vascular tension analyses reveals molecular targets and phenotypes in preeclamptic placental vasculature

IntroductionThe placental vascular system plays an important role in the development of pregnancy hypertension in preeclampsia. The gene profiles of whole placental tissue (containing blood vessels and many other structural components) and pure vascular tissue should be very different. All previous reports using RNA-seq analysis in the placenta have tested its whole tissue or the villous part, and thus the gene profiles in the pure placental blood vessels are unknown.MethodsThis study was the first to address this point with RNA-seq in human placenta at the transcript level. Isolated placental micro-vessels from normal and preeclamptic pregnancies were used for RNA-seq analysis, real-time quantitative polymerase chain reaction (RT-qPCR) verification, and vascular function tests. Furthermore, a vascular function-centric core network was constructed to show the gene-gene interactions and gene-function associations in the placental vessel system.ResultsDifferential expression analysis identified a total of 486 significantly changed transcripts. Bioinformatics analysis further confirmed that multiple genes were highly related to blood vessel and placental phenotypes. Several hub genes, including ELMO1, YWHAE, and IL6ST, were significantly reduced in the placental vessels in preeclampsia. Vascular tension experiments showed that angiotensin II-mediated vasoconstriction and exogenous NO donor sodium nitroprusside-induced vasodilation were decreased, while phenylephrine-mediated vascular responses were unchanged in placental micro-vessels in preeclampsia.DiscussionThe results provide important insights into the pathological process in the placental vasculature in preeclampsia and offer great potential for further investigation of these molecular targets in the human placental vascular system.

Serum Magnesium concentration in normal and preeclamptic pregnancy: A tertiary center experience

Preeclampsia and maternal mortality are more prevalent in underdeveloped nations. Preeclampsia has an estimated 16% incidence rate in Bangladesh, which is extremely high. One of the body's major macronutrients is magnesium. It also serves a multitude of enzymes as a cofactor. This cross-sectional study was done in the department of Biochemistry of Mymensingh Medical College, Mymensingh, from July 2016 to June 2017. This study involved a total of 100 individuals, where 50 preeclamptic patients and 50 healthy pregnant women served as the case and control groups, respectively. The results were shown as mean ±SD. For both the case and control groups, the mean ±SD of serum magnesium levels were 1.75 ±0.22 mg/dl and 1.63 ±0.21, respectively. Comparison of the mean ±SD of serum magnesium in the case and control groups revealed a highly significant difference (P<0.001). Students' unpaired ‘t’ test was used to compute the statistical difference. Mediscope 2024;11(2): 73-76

Altered placental expression of genes related to Vitamin D Metabolism and their correlation with spiral artery remodeling in Preeclamptic Women

Background: Several studies reveals the correlation of preeclampsia (PE) with low vitamin D (VD) level due to disturbed trophoblast invasion and failure of spiral artery remodeling. The metabolism of VD is regularized by it signaling molecules expressed by the placenta during pregnancy. Therefore, this study was designed to assess and compare the levels of VD and it signaling molecules in placentae from normotensive and preeclamptic pregnancies and their correlation with spiral artery remodeling.Methods: This study was carried out at Department of Anatomy at Liaquat University of Medical & Health Sciences, Jamshoro after ethical approval on placentae of 122 parturients; 61 from normal and 61 from preeclampsia, data was collected on predesigned proforma and was analyzed on SPSS 23.Results: The mean and standard deviation of maternal age, gestational age, and parity was 32.73±5.9 years, 37.3±3.6 weeks and 3±1 respectively. The wall thickness of SA and VD when compared in two groups found statically significant. Vitamin D signaling molecules were determined by immunostaining compared in two groups by applying Mann Whitney U test and Pearson’s correlation which reveals significant differences in preeclamptic versus controls.Conclusions: Despite extensive research indicating a link between low levels of VD and its signaling molecules in the context of inadequate spiral artery remodeling, there is still a need for further investigation to fully understand the mechanisms underlying this association in preeclampsia.Keywords: Preeclampsia; Remodeling; Spiral artery; Vitamin D; Vitamin D signaling molecules

Decidual Granulomas in Placenta: A unique finding in Preeclamptic Pregnancy

Abstract Introduction/Objective Decidual granulomatous inflammation is a rare finding in the placenta, scarcely reported in the literature. We present an unusual case of a young woman with severe preeclampsia and histological presence of decidual granuloma, involving the placental membranes. Methods/Case Report A 34-year-old female, Gravida 2 Para 1, with prior term vaginal delivery without significant history presented at 26 weeks and 6 days of gestational age with decreased fetal movements. Her home blood pressure was 170 mm of Hg systolic and on presentation, was consistently within the range of <a href=“tel:192- 197/94-97”>192-197/94-97</a> mm of Hg. Biophysical profile of the fetus was 2/10. Complete blood count showed leukocytosis with absolute neutrophilia and urinalysis revealed slight increase in urine protein/creatinine ratio. Clinical diagnosis of severe preeclampsia was made. After initial stabilization, the patient underwent Cesarean section resulting in a premature baby with an uneventful postoperative course. The placenta was sent for histopathological examination. Grossly, the placental disc showed unremarkable membranes with normal appearing fetal and maternal surfaces. Sectioning revealed a central 4.2 cm hemorrhagic area and six tan-white wedge-shaped nodules ranging from 0.8-1.8 cm, occupying approximately 5% and 40% of the maternal surface, respectively. Microscopic examination revealed patchy non-caseating granulomas limited to the decidua, patchy intra-placental hematomas, placental infarcts and chronic villitis. Other findings included scattered avascular villi, villous stromal vascular karyorrhexis, focally increased syncytial knots, and decidual arteriopathy. Gram stain, GMS and acid-fast stains yielded negative results, while immunohistochemical stain CD68 highlighted histiocytes in the granulomas. The final diagnosis of decidual granulomas including the aforementioned microscopic observations was made. Results (if a Case Study enter NA) NA Conclusion Though decidual granulomas are seen in association with infectious and rheumatologic disorders. They can also be observed in severe preeclampsia as in this setting; with unclear underlying pathogenesis, warranting a close follow-up of the newborn and the mother.

SFlt-1/PLGF ratio: A promising marker for early detection of preeclampsia in the second and third trimester

: Preeclampsia (PE), characterized by endothelial dysfunction, remains a significant concern in obstetrics due to its association with maternal and fetal morbidity and mortality. One significant contributor to the clinical manifestations of PE is the imbalance in the placental release of various angiogenesis regulatory factors into the maternal circulation. Low levels of the pro-angiogenic biomarker Placental Growth Factor (PLGF) and high levels of antiangiogenic biomarker sFlt-1 (soluble Fms like tyrosine kinase -1) levels are detectable several weeks before the clinical presentation of PE, making them a promising marker for early diagnosis.: This study investigates the utility of the sFlt-1/PLGF ratio in predicting and diagnosing preeclampsia during the second and third trimesters of pregnancy.: A prospective cohort study was conducted with 150 study participants comprising normotensive controls and preeclamptic cases, diagnosed based on blood pressure and proteinuria criteria. Serum samples collected in the second trimester (24-28 weeks) and third trimester (>28 weeks) were analyzed for PLGF and sFlt-1 levels using ELISA kit method. The sFlt-1/PLGF ratio was calculated and evaluated for its diagnostic accuracy through ROC curve analysis.: Significantly lower PLGF levels and higher sFlt-1 levels in preeclamptic pregnancies compared to normotensive pregnancies were seen in both trimesters (p < 0.001). The sFlt-1/PLGF ratio was markedly elevated in preeclampsia, showing strong predictive characteristics with an AUC of 0.929 (sensitivity 90%, specificity 90%) in the second trimester and an AUC of 0.986 (sensitivity 90%, specificity 96.7%) in the third trimester. These findings highlight the potential of the sFlt-1/PLGF ratio as a biomarker for early detection and risk stratification in pregnancies complicated by preeclampsia.

Maternal Microvascular Dysfunction During and After Preeclamptic Pregnancy.

Preeclampsia, a pregnancy disorder characterized by de novo hypertension and maternal multisystem organ dysfunction, is the leading cause of maternal mortality worldwide and is associated with a fourfold greater risk of cardiovascular disease throughout the lifespan. Current understanding of the etiology of preeclampsia remains unclear, due in part to the varying phenotypical presentations of the disease, which has hindered the development of effective and mechanism-specific treatment or prevention strategies both during and after the affected pregnancy. These maternal sequelae of preeclampsia are symptoms of systemic vascular dysfunction in the maternal nonreproductive microvascular beds that drives the development and progression of adverse cardiovascular outcomes during preeclampsia. Despite normalization of vascular disturbances after delivery, subclinical dysfunction persists in the nonreproductive microvascular beds, contributing to an increased lifetime risk of cardiovascular and metabolic diseases and all-cause mortality. Given that women with a history of preeclampsia demonstrate vascular dysfunction despite an absence of traditional CVD risk factors, an understanding of the underlying mechanisms of microvascular dysfunction during and after preeclampsia is essential to identify potential therapeutic avenues to mitigate or reverse the development of overt disease. This article aims to provide a summary of the existing literature on the pathophysiology of maternal microvascular dysfunction during preeclampsia, the mechanisms underlying the residual dysfunction that remains after delivery, and current and potential treatments both during and after the affected pregnancy that may reduce microvascular dysfunction in these high-risk women. © 2024 American Physiological Society. Compr Physiol 14:5703-5727, 2024.

Frequent Use of Premenopausal Progestin in Prior Pre-Eclamptic Women.

Women with a history of pre-eclamptic pregnancy are predisposed to later occlusive vascular diseases. We compared the use of cyclic progestins or levonorgestrel-releasing intrauterine device (LNG-IUD) for treatment of menstrual cycle abnormalities between premenopausal women with and without a prior pre-eclamptic pregnancy. Register-based cohort study during 1994-2019 of oral progestin or levonorgestrel-releasing intrauterine device (LNG-IUD) in Finnish women with (n=31 688) and without (n=91 726) prior pre-eclampsia in 1969-1993. Cyclic progestin or LNG-IUD use and its association with future use of menopausal hormone therapy (MHT). Prior pre-eclamptic women had used cyclic progestins more often (23.5% vs. 9.1%; p<0.001) and initiated the use at younger ages (41.8 years [SD=6.3] vs. 45.9 years [3.1]; p<0.001) than control women. Also, LNG-IUD was inserted more frequently (p<0.001) in prior pre-eclamptic women (9.3%) than in controls (4.7%). Cyclic progestin or LNG-IUD use was accompanied by significant 37-90% elevations in future MHT use. Increased use of cyclic progestins and LNG-IUD in premenopausal women with a history of pre-eclamptic pregnancy can be seen as indirect evidence of earlier onset of ovulatory dysfunction. This may contribute to the elevated risk of endometrial cancer in these women. Our findings may indicate one additional late sequela of pre-eclamptic pregnancy.

Oocyte donation pregnancies with high fetal-maternal immunogenetic dissimilarity show alterations in the maternal peripheral immunoregulatory response

Oocyte donation (OD) pregnancies result in increased fetal-maternal immunogenetic dissimilarity due to paternal and donor-derived genes. Higher fetal-maternal HLA mismatches are correlated with preeclampsia. Therefore, this study explored the maternal immune response, focusing on regulatory T cells (Tregs), during low versus high allogeneic pregnancies, and healthy versus preeclamptic OD pregnancies. Ten healthy and five preeclamptic OD pregnancies were included. Maternal peripheral blood was collected at different stages of pregnancy. Fetal-maternal HLA mismatches were determined, and immunophenotyping of peripheral blood mononuclear cells was conducted using a 22-colour spectral flow cytometry panel. Cytokines and hormones were detected in maternal plasma using ELISA and Luminex assays. The findings show similarities, but also distinct differences between low and high allogeneic healthy OD pregnancies. Early high allogeneic OD pregnancy showed reduction in Tregs, and CD8+ T cells, alongside lower percentage of effector/memory Tregs expressing PD-1 and Helios. Additionally, high allogeneic OD pregnancies showed increased IL-6 and progesterone in the first trimester. These variations suggest a different mode of immune regulation in early high allogeneic OD pregnancies, possibly to maintain healthy pregnancy. Further comparative analyses revealed reduced CD45RO+CTLA-4+ Tregs and increased latent TGF-β1 and -β2 levels in early preeclamptic compared to healthy OD pregnancy. Late-stage preeclamptic OD pregnancies exhibited higher frequencies of CD45RO+TIGIT+ Tregs and higher levels of TNFα, indicating both a regulatory and pro-inflammatory environment. Overall, this study sheds light on the course of various immunoregulatory key players in OD pregnancy, and expands knowledge on maternal tolerance in this particular type of pregnancy.

Abstract P197: Identification and Characterization of Rho-related BTB Domain Containing 1 (RhoBTB1)-Cullin 3 (CUL3) Proteins in Placenta

Preeclampsia is life threatening condition affecting about 10% of all pregnancies. A potential mechanism is via malfunctioning syncytiotrophoblasts in the placenta. RhoBTB1 is an adapter protein for the CUL3 E3 ubiquitin ligase which delivers protein substrates for proteasomal degradation. An analysis of gene expression databases revealed that the highest level of RhoBTB1 expression is in the placenta. RNAscope in situ hybridization data reveals that RhoBTB1 expression is specifically localized to syncytiotrophoblasts. In blood vessels, RhoBTB1 controls the state of nitric oxide mediated vasodilation because it acts as a substrate adaptor for Phosphodiesterase 5. Thus, we wanted to identify potential protein targets of RhoBTB1 in the placenta to assess if RhoBTB1 plays a role in placental function. To simplify the first identification of RhoBTB1 binding proteins, we employed HTR-8 /SVneo (HTR-8) cells as a model of placental trophoblast cells. We biotinylated the HTR-8 proteome utilizing ascorbate peroxidase (APEX2) proximity labelling system followed by mass spectrometry to identify RhoBTB1 targets. We employed a fusion protein consisting of the C-terminal half of RhoBTB1 (B1B2C), the region required for the binding of other protein substrates, and a control lacking the most C-terminal region (B1B2). We next chose proteins with binding to B1B2C &gt; B1B2 of 2-fold or greater that were expressed in the placenta based on the Human Protein Atlas. Rho GTPase Activating Protein 29 (ARHGAP29), which controls the regulation of small GTP binding proteins, and S-phase Kinase associated Protein 2 (SKP2), a regulator of cell cycle progression was studied further. SKP2 is interesting because it exhibits a tissue specific tropism for placental expression with its highest expression in extravillous trophoblasts, cytotrophoblasts, and syncytiotrophoblasts. Expression of ARHGAP29 and SKP2 in HTR-8 cells were markedly upregulated by MLN4924 suggesting they are regulated by the CUL pathway. They were also modestly upregulated after partial inhibition of RhoBTB1 by siRNA suggesting they may be RhoBTB1-CUL3 targets. Studies are ongoing to validate the physical interaction of ARHGAP29 and SKP2 with RhoBTB1 by co-immunoprecipitation. We are also using RNAscope to assess the co-expression of RhoBTB1, ARHGAP29 and SKP2 in the human placenta from normal and preeclamptic pregnancies.

Abstract MP29: Preeclampsia Dysregulates The MicroRNA Profile Of Small Extracellular Vesicles From Endothelial Colony Forming Cells

Umbilical cord blood contains an enriched population of endothelial colony forming cells (ECFCs), which are vital for de novo vasculogenesis and vessel homeostasis. Previously, our lab has shown that preeclampsia (PE), a hypertensive disorder of pregnancy seen after 20 weeks of gestation, causes perturbations in how the ECFCs function, including decreased vasculogenic potential, and could cause increased risks to the infant later in life. Developing methods to monitor and restore the changes in these cells could significantly improve fetal outcomes. One such method is monitoring small extracellular vesicles (sEVs), which contain a cargo of RNA, DNA, and proteins that can influence other cell’s function through paracrine signaling. By quantifying microRNA (miRNA) expression in the PREC sEVs, we aim to identify potential biomarkers and determine their ability to restore PREC functionality. ECFCs from healthy (ECFCs) and preeclamptic (PRECs) pregnancies were isolated from cord blood. Three low passage (P4-5) and three high passage (P7-8) cell lines were used for each condition. The supernatant from each cell type was collected, filtered, and ultracentrifuged to isolate the sEVs. The miRNA isolated from the sEVs was quantified using the Nanostring nCounter. Results were assessed using nSolver for data normalization, R for differential expression, and MetaCore for pathway analysis. High and low passage ECFC sEVs were added to the media of the PRECs (1x10 8 sEVs/mL). After 24 hours of treatment, a tube formation assay was run. There is significant dysregulation of miRNA in the PRECs compared to the ECFCs. Most of the miRNA were associated with proliferation, gene transcription, migration, and angiogenesis. In addition, there are some PE associated functions affected including endometrial remodeling, decidualization, and embryonic development. After treating the PRECs with ECFC exosomes of high and low passages, the PRECs had a more distinct network with clear loops and more branching compared to the untreated control. PE causes a distinct miRNA profile in PRECs. This data suggests that the dysregulated profile could be used as biomarkers to assess the progression of PE as some miRNA was identified in high or low passage only as well as provide a method for earlier diagnosis. In addition, treatment with healthy sEVs improving PREC tube forming ability indicates their potential as a therapeutic for enhancing vascularization post-PE and improving perinatal outcomes.

Leukocyte-associated immunoglobulin-like receptor 1 (LAIR1) is reduced with preeclampsia and small for gestational aged fetuses

Leukocyte-associated immunoglobulin-like receptor 1 (LAIR1) is an inhibitory receptor expressed on immune cells. We evaluated LAIR1 in placentas from preeclamptic or small for gestational age (SGA) pregnancies, and placental explant model (1 % O2, IL6 and TNFα, or control). LAIR1 mRNA was reduced in placentas from preeclamptic (p < 0.0001, n = 78) and SGA (p < 0.0001, n = 32) pregnancies. LAIR1 protein expression was reduced in placentas from preeclampsia (p < 0.0001, n = 43) and SGA (p = 0.009, n = 10) pregnancies. Hypoxia (1 % O2) reduced LAIR1 mRNA expression in placental explants (p = 0.008). These findings suggest hypoxia modulates LAIR1 expression in the placenta.

A Novel Stem Cell Model to Study Preeclampsia Endothelial Dysfunction

Preeclampsia is a common pregnancy complication affecting 5% to 7% of all pregnancies worldwide annually. While the pathogenesis is not fully understood, maternal endothelium dysfunction is thought to be a central component to preeclampsia development. Studies to dissect maternal endothelial dysfunction, particularly on a patient-specific basis, are hampered by limited access to systemic primary endothelial cells (ECs). The objective of this study was to establish a replenishable, patient-specific in vitro EC model to allow robust mechanistic studies to dissect endothelial dysfunction in preeclampsia. Induced pluripotent stem cells (iPSCs) from three women with a history of normotensive pregnancies were differentiated into ECs. The established ECs were exposed to pooled sera from normotensive pregnancies, preeclamptic pregnancies, normotensive postpartum for non-pregnant comparison and controls. Endothelial functions including nitric oxide (NO) release, cell migration, tube formation and viability were evaluated. Levels of NO release were significantly lower after incubation with preeclamptic sera compared to the fetal bovine serum (FBS) control, and normotensive and non-pregnant (postpartum) sera treatments were also lower than FBS but higher than preeclamptic sera treatments. Tube formation and cell migration were also impaired with preeclamptic sera compared to FBS controls. Cell viabilities remained unaffected by any sera treatment. Consistent outcomes were obtained across all three patient-specific lines treated with the same pooled sera. Establishment of patient-derived iPSC-ECs treated with pregnancy sera serves as a novel model to explore the interplay between individual maternal endothelial health and circulating factors that lead to endothelial dysfunction in preeclampsia.

Five-Feature Models to Predict Preeclampsia Onset Time From Electronic Health Record Data: Development and Validation Study.

Preeclampsia is a potentially fatal complication during pregnancy, characterized by high blood pressure and the presence of excessive proteins in the urine. Due to its complexity, the prediction of preeclampsia onset is often difficult and inaccurate. This study aimed to create quantitative models to predict the onset gestational age of preeclampsia using electronic health records. We retrospectively collected 1178 preeclamptic pregnancy records from the University of Michigan Health System as the discovery cohort, and 881 records from the University of Florida Health System as the validation cohort. We constructed 2 Cox-proportional hazards models: 1 baseline model using maternal and pregnancy characteristics, and the other full model with additional laboratory findings, vitals, and medications. We built the models using 80% of the discovery data, tested the remaining 20% of the discovery data, and validated with the University of Florida data. We further stratified the patients into high- and low-risk groups for preeclampsia onset risk assessment. The baseline model reached Concordance indices of 0.64 and 0.61 in the 20% testing data and the validation data, respectively, while the full model increased these Concordance indices to 0.69 and 0.61, respectively. For preeclampsia diagnosed at 34 weeks, the baseline and full models had area under the curve (AUC) values of 0.65 and 0.70, and AUC values of 0.69 and 0.70 for preeclampsia diagnosed at 37 weeks, respectively. Both models contain 5 selective features, among which the number of fetuses in the pregnancy, hypertension, and parity are shared between the 2 models with similar hazard ratios and significantPvalues. In the full model, maximum diastolic blood pressure in early pregnancy was the predominant feature. Electronic health records data provide useful information to predict the gestational age of preeclampsia onset. Stratification of the cohorts using 5-predictor Cox-proportional hazards models provides clinicians with convenient tools to assess the onset time of preeclampsia in patients.

Serum CA 125 in normal and preeclamptic pregnancies

Serum CA 125 in normal and preeclamptic pregnancies

Exploring the Therapeutic Potential of C-Type Natriuretic Peptide for Preeclampsia.

Preeclampsia is a serious condition of pregnancy, complicated by aberrant maternal vascular dysfunction. CNP (C-type natriuretic peptide) contributes to vascular homeostasis, acting through NPR-B (natriuretic peptide receptor-B) and NPR-C (natriuretic peptide receptor-C). CNP mitigates vascular dysfunction of arteries in nonpregnant cohorts; this study investigates whether CNP can dilate maternal arteries in ex vivo preeclampsia models. Human omental arteries were dissected from fat biopsies collected during cesarean section. CNP, NPR-B, and NPR-C mRNA expression was assessed in arteries collected from pregnancies complicated by preeclampsia (n=6) and normotensive controls (n=11). Using wire myography, we investigated the effects of CNP on dilation of arteries from normotensive pregnancies. Arteries were preconstricted with either serum from patients with preeclampsia (n=6) or recombinant ET-1 (endothelin-1; vasoconstrictor elevated in preeclampsia; n=6) to model vasoconstriction associated with preeclampsia. Preconstricted arteries were treated with recombinant CNP (0.001-100 µmol/L) or vehicle and vascular relaxation assessed. In further studies, arteries were preincubated with NPR-B (5 µmol/L) and NPR-C (10 µmol/L) antagonists before serum-induced constriction (n=4-5) to explore mechanistic signaling. CNP, NPR-B, and NPR-C mRNAs were not differentially expressed in omental arteries from preeclamptic pregnancies. CNP potently stimulated maternal artery vasorelaxation in our model of preeclampsia (using preeclamptic serum). Its vasodilatory actions were driven through the activation of NPR-B predominantly; antagonism of this receptor alone dampened CNP vasorelaxation. Interestingly, CNP did not reduce ET-1-driven omental artery constriction. Collectively, these data suggest that enhancing CNP signaling through NPR-B offers a potential therapeutic strategy to reduce systemic vascular constriction in preeclampsia.

Implications of pregnancy on cardiometabolic disease risk: preeclampsia and gestational diabetes.

Cardiometabolic disorders, such as obesity, insulin resistance, and hypertension, prior to and within pregnancy are increasing in prevalence worldwide. Pregnancy-associated cardiometabolic disease poses a great risk to the short- and long-term well-being of the mother and offspring. Hypertensive pregnancy, notably preeclampsia, as well as gestational diabetes are the major diseases of pregnancy growing in prevalence as a result of growing cardiometabolic disease prevalence. The mechanisms whereby obesity, diabetes, and other comorbidities lead to preeclampsia and gestational diabetes are incompletely understood and continually evolving in the literature. In addition, novel therapeutic avenues are currently being explored in these patients to offset cardiometabolic-induced adverse pregnancy outcomes in preeclamptic and gestational diabetes pregnancies. In this review, we discuss the emerging pathophysiological mechanisms of preeclampsia and gestational diabetes in the context of cardiometabolic risk as well as the most recent preclinical and clinical updates in the pathogenesis and treatment of these conditions.

Inhibition of autophagy via 3-methyladenine alleviates the progression of preeclampsia.

Autophagy is a cellular mechanism for self-renewal that involves the breakdown of cytoplasmic proteins or organelles within lysosomes. Although preeclampsia (PE) exhibits several characteristics that could imply disrupted autophagy, there is limited evidence supporting the notion that impaired placental autophagy directly causes PE, as indicated by differential expression profiling of whole placental tissue. In this study, we aim to explore the significance of autophagy in maintaining pregnancy and its association with PE. First, the RNA-seq results show that 218 genes are differentially expressed in placentas from preeclamptic pregnancies. Notably, KEGG pathway analysis reveals significant enrichment of genes related to autophagy-related signaling pathways, including the PI3K-Akt signaling pathway, the AMPK signaling pathway, and the mTOR signaling pathway. Additionally, our findings indicate an increase in autophagy in placentas from pregnancies complicated by preeclampsia as well as in trophoblasts subjected to hypoxic conditions. Next, we examine the impact of 3-methyladenine (3-MA), a targeted inhibitor of autophagy, on the progression of PE. The administration of 3-MA profoundly alleviates the severity of PE-like symptoms in rats subjected to reduced uterine perfusion pressure (RUPP). The findings from our study suggest that inhibiting autophagy may serve as a promising approach for adjuvant chemotherapy for PE.

Placental Protein 13 and Syncytiotrophoblast Basement Membrane Ultrastructures in Preeclampsia.

Background and Objectives: Preeclampsia has been linked to an inflammatory response that may be brought on by endothelial cell dysfunction. This paper investigates the pathomechanism of syncytiotrophoblast basement membrane (STBM) damage and Placental Protein 13 (PP13) release, which may have a role in systemic endothelial dysfunction in preeclampsia. Materials and Methods: This comparative cross-sectional study involves 54 preeclampsia patients (27 early-onset preeclampsia and 27 late-onset preeclampsia) and 27 pregnant women with normal blood pressure. An enzyme-linked immunosorbent assay was performed to evaluate maternal blood levels of PP13. Following birth, a portion of the placenta was collected for transmission electron microscope (TEM) and immunohistochemical (IHC) analysis. The data were analyzed using STATA version 15. Results: PP13 expression in the placental syncytiotrophoblast was significantly lower in the early-onset preeclampsia, compared to late-onset preeclampsia and normotensive pregnancy, group (p < 0.001). In contrast, serum PP13 levels were found to be the highest in the early-onset preeclampsia group, although no significant difference were found in mean maternal serum levels of PP13 between the three groups. The decreased PP13 expression in placental syncytiotrophoblast can be attributed to the greater extent of damage in the STBM in early-onset preeclampsia that leads to the release of a larger amount of PP13 into maternal circulation. The hypothesis aligns with the TEM analysis results. Preeclamptic pregnancies showed placental syncytiotrophoblast aponeurosis, whereas normotensive pregnancies did not. Placental lesions and STBM shedding were found to be more pronounced in early-onset preeclampsia compared to late-onset preeclampsia. Conclusions: PP13 and STBM damage may play a role in systemic endothelial dysfunction in preeclampsia.

Decreased postpartum exercise capacity after a diagnosis of pre-eclampsia: Implications for CVD risk prediction

BackgroundHypertensive disorders of pregnancy (HDP) are associated with increased long-term risk for cardiometabolic risk factors (chronic hypertension [HTN], obesity, diabetes) and heart failure. Exercise capacity is a known predictor of heart failure in patients with normal resting cardiac filling pressures. In this prospective observational cohort study, we sought to identify predictors of reduced postpartum exercise capacity in participants with normotensive vs. preeclamptic pregnancies. MethodsPreeclampsia (PreE) and normotensive subjects were enrolled to undergo bedside echocardiography within 48 hours of delivery, and rest/exercise echocardiography 12 weeks postpartum. ResultsRecruited subjects (n=68) were grouped according to their blood pressure as: a) normotensive pregnancy n=15; b) PreE with normotensive postpartum (PreE-Resolved, n=36); c) PreE with persistent postpartum HTN (PreE-HTN, n=17). At enrollment, a significantly higher percentage of subjects in the PreE-HTN group were Black. Compared to normotensive and PreE-Resolved subjects, those with PreE-HTN demonstrated higher resting systolic blood pressure (SBP, 112 [normotensive] vs 112 [PreE-Resolved] vs 134 [PreE-HTN], p<0.001) and diastolic blood pressure (DBP, 70.0 vs 72.5 vs 85.0, p<0.001), and significantly less postpartum weight loss (9.6% vs 13.6% vs 3.8%, p<0.001). Following Bruce protocol stress testing, PreE-HTN subjects demonstrated achieved significantly lower exercise duration (10.4 vs 10.2 vs 7.9 minutes, p = 0.001). Subjects with PreE-HTN also demonstrated evidence of exercise-induced diastolic dysfunction as assessed by peak exercise lateral e’ (18.0 vs 18.0 vs 13.5, p=0.045) and peak exercise tricuspid regurgitation velocity (TR Vm, 2.4 vs 3.0 vs 3.1, p = 0.045). Exercise duration was negatively associated with gravidity (R=-0.27, p=0.029) and postpartum LV mass index (R=-0.45, p<0.001), resting average E/e’ (R=-0.51, p<0.001), BMI (R=-0.6, p<0.001) and resting SBP (R=-0.51, p<0.001). ConclusionsPostpartum exercise stress testing capacity is related to readily available clinical markers including pregnancy factors, echocardiographic parameters and unresolved cardiometabolic risk factors.

SDMS CME Credit – Correlation Between Fetal Umbilical Artery and Middle Cerebral Artery Doppler Indices in Preeclamptic and Normotensive Pregnancies

SDMS CME Credit – Correlation Between Fetal Umbilical Artery and Middle Cerebral Artery Doppler Indices in Preeclamptic and Normotensive Pregnancies