Higher sFlt-1 Levels Research Articles

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 Thyroid Function and Biochemical Markers of Placental Function in Early Pregnancy.

A link between maternal thyroid function and the placental biomarkers, soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF), has been brought forward. This study aimed to describe their association in early pregnancy. Retrospective cohort study. Eight hundred and fifty-eight pregnant women from the North Denmark Region, 2013, with blood samples drawn in early pregnancy. Thyroid-stimulating hormone (TSH), free thyroxine (fT4), thyroid-peroxidase antibodies (TPO-Ab), thyroglobulin antibodies (Tg-Ab) (ADVIA Centaur XPT, Siemens Healthineers), sFlt-1 and PlGF (Kryptor Compact, ThermoFisher Scientific) were measured. The association between maternal TSH and fT4 and percentile (pc) levels of sFlt-1 and PlGF (< 25th pc, 25-75th pc, > 75th pc) was evaluated using regression analysis and reported as adjusted beta coefficient (aβ). The frequency of maternal thyroid autoantibodies (TPO-Ab > 60 U/mL or Tg-Ab > 33 U/mL) by pc levels of sFlt-1 and PlGF was compared using chi-squared test. Higher levels (> 75th pc) of sFlt-1 associated with lower TSH (aβ 0.62, 95% CI: 0.51-0.76) and higher fT4 (aβ 1.03, 95% CI: 1.01-1.05). Higher levels of PlGF associated with lower TSH (aβ 0.82, 95% CI: 0.69-0.98), but not with levels of fT4 (aβ 1.00, 95% CI: 0.97-1.02). No association with maternal thyroid autoantibodies was found (TPO-Ab: sFlt-1: p-value 0.5 and PlGF: p-value 0.1; Tg-Ab: sFlt-1: p-value 0.7 and PlGF: p-value 0.1). In a large cohort of Danish pregnant women, higher levels of sFlt-1 and PlGF associated with maternal thyroid function in early pregnancy, while there was no association with maternal thyroid autoantibodies.

Utility of placental biomarkers and fetoplacental Dopplers in predicting likely placental pathology in early and late fetal growth restriction – A prospective study

IntroductionThe aim of this study was to evaluate the association between placental abnormalities, placental biomarkers, and fetoplacental Dopplers in a cohort of pregnancies complicated by fetal growth restriction (FGR). We also ascertained the risk of perinatal mortality, severe neurological morbidity, and severe non-neurological morbidity by type of placental abnormality. MethodsThis was a prospective cohort study. Multivariable logistic regression was used to evaluate the effect of early vs. late FGR, placental biomarkers and fetoplacental Dopplers on Maternal Vascular Malperfusion (MVM) which was the commonest placental abnormality identified. ResultsThere were 161 (53.5 %) early FGR and 140 (46.5 %) late FGR cases. MVM abnormalities were present in 154 (51.2 %), VUE in 45 (14.6 %), FVM in 16 (5.3 %), DVM in 14 (4.7 %) and CHI in 4 (1.3 %) cases. The odds of MVM were higher in early compared to late FGR cohort (OR 1.89, 95%CI 1.14, 3.14, p = 0.01). Low maternal PlGF levels <100 ng/L (OR 2.34, 95%CI 1.27,4.31, p = 0.01), high sFlt-1 level (OR 2.13, 95%CI 1.35, 3.36, p = 0.001) or elevated sFlt-1/PlGF ratio (OR 3.48, 95%CI 1.36, 8.91, p = 0.01) were all associated with MVM. Increased UA PI > 95th centile (OR 2.91, 95%CI 1.71, 4.95, p=<0.001) and mean UtA PI z-score (OR 1.74, 95%CI 1.15, 2.64, p = 0.01) were associated with higher odds of MVM. Rates of severe non-neurological morbidity were highest in the MVM, FVM, and CHI cohorts (44.8 %, 50 %, and 50 % respectively). ConclusionMVM was the commonest placental abnormality in FGR, particularly in early-onset disease. Low maternal PlGF levels, high sFlt-1 levels, elevated sFlt-1/PlGF ratio, and abnormal fetoplacental Dopplers were also significantly associated with MVM. MVM, FVM, and CHI abnormalities were associated with lower median birthweight, higher rates of preterm birth, operative birth for non-reassuring fetal status, and severe neonatal non-neurological morbidity.

Soluble Fms-like tyrosine kinase-1 as an endothelial dysfunction biomarker associated with pulmonary hypertension in adult patients with beta-thalassemia major.

The etiology of vascular problems in beta-thalassemia has been linked to endothelial damage. Antiangiogenic proteins such as soluble Fms-like tyrosine kinase-1 (sFLT-1) inhibit the signaling of vascular endothelial growth factor and placental growth factor, resulting in a decrease in the development of new blood vessels. Additionally, they promote the maturation of existing blood vessels and lead to endothelial dysfunction. This study aimed to assess the role of sFLT-1 in adult patients with beta-thalassemia major (TM) as a biomarker of endothelial dysfunction and its association with pulmonary hypertension (PHT). A total of 90 subjects were recruited and categorized into two groups: 45 patients with beta-TM, who were further divided based on the presence or absence of PHT, and 45 healthy individuals served as a control group. Serum sFLT-1 was determined using the enzyme-linked immunosorbent assay technique. The results revealed that Beta-TM patients had higher sFLT-1 levels than the control group. In addition, patients with PHT had significantly higher sFLT-1 levels compared to those without PHT. The levels of sFLT-1 were positively correlated with von Willebrand factor, serum ferritin, and high-sensitivity C-reactive protein. Regression analyses demonstrated a significant association between high sFLT-1 levels and the occurrence of PHT. Additionally, sFLT-1 (at a cutoff value of 8.84 pg/mL) demonstrated a sensitivity of 83.30% and a specificity of 80.0% in diagnosing thalassemic patients with PHT. In conclusion, beta-TM patients with elevated serum levels of sFLT-1 are at risk of developing endothelial dysfunction and subsequent development of PHT.

The sFlt1/PIGF Ratio Predicts Faster Fetal Deterioration in Early Fetal Growth Restriction: A Historical Cohort Study

(Acta Obstet Gynecol Scand. 2023;102:635–643) Both placental growth factor (PlGF) and tyrosine kinase 1 (sFlt1) are predicted to be factors in impaired placentation, which is known to lead to diseases such as pre-eclampsia and fetal growth restriction (FGR). Previous studies have shown fluctuations in the levels of PlGF and sFlt1 in patients with these diseases. This study aimed to determine the effects that high levels of PlGF and sFlt1 have on the deterioration of FGR in neonates.

SFlt-1 Levels as a Predicting Tool in Placental Dysfunction Complications in Multiple Pregnancies.

several studies have demonstrated that angiogenic markers can improve the clinical management of hypertensive disorders (HDs) and fetal growth restriction (FGR) in singleton pregnancies, but few studies have evaluated the performance of these tests in multiple pregnancies. Our aim was to investigate the role of soluble fms-like tyrosine kinase 1 (sFlt-1) in predicting adverse obstetric outcomes in hospitalized multiple pregnancies with HD (preeclampsia/gestational hypertension/uncontrolled chronic hypertension) and/or FGR in one or more fetuses. A retrospective analysis of multiple pregnancies with HD/FGR occurring after the 20th gestational week. Pregnant women were divided into two groups: women with high levels of sFlt-1 and those with low levels of sFlt-1. A value of sFlt-1 greater than or equal to 15,802 pg/mL was considered arbitrarily high, as it is equivalent to two times the 90th percentile expected in an uncomplicated full-term singleton pregnancy based on data from a prospective multicenter study (7901 pg/mL). The cohort included 39 multiple pregnancies. There were no cases of birth <34 weeks, HELLP syndrome, ICU admission, and urgent cesarean sections for HD/FGR complications reported among women with low levels of sFlt-1. A cut-off value of sFlt-1 ≥ 15,802 pg/mL could represent a valuable tool for predicting adverse obstetric outcomes in multiple pregnancies hospitalized for HD/FGR disorders, regardless of gestational age and chorionicity.

HIGH SERUM RATIO OF SOLUBLE FMS-LIKE TYROSINE KINASE 1 (sFlt-1) TO PLACENTAL GROWTH FACTOR (PIGF) AND HIGH LEVEL OF LOW-DENSITY LIPOPROTEIN (LDL) AS RISK FACTORS OF PREECLAMPSIA

Preeclampsia is an obstetric disease that is a health problem worldwide, including in Indonesia. Several studies have shown that changes in the maternal spiral arteries are thought to lead to preeclampsia. Preeclampsia in this decade has been associated with changes in angiogenesis regulatory proteins originating from the placenta and circulating in the mother's blood circulation, namely soluble FMS-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PlGF). The author was interested in examining the ratio of sFlt-1/PIGF and low-density lipoprotein (LDL) to the incidence of preeclampsia in pregnant women. This study used a case control analytic observational design. The research sample was selected by consecutive sampling of 20 cases and 20 controls. Univariate analysis was used to describe patient characteristics descriptively, and bivariate analysis was used to determine the relationship between the 2 variables There is no significant difference in the characteristics of the research subjects. Low PIGF levels are a risk factor for preeclampsia (OR 4.33; p 0.0302) with a cut-off value of 24.5. High sFlt-1 levels are a risk factor for preeclampsia (OR 4.33; p 0.027) with a cut-off value of 869.5. A high sFlt-1/PIGF ratio is a risk factor for preeclampsia (OR 4.33 p 0.030) with a cut-off value of 38. High LDL levels are a risk factor for preeclampsia (OR 6.0; p 0.013) with a cut-off value of 150 ,2. Low placental growth factor (PIGF), high levels of soluble FMS-like tyrosine kinase 1 (sFlt-1), and high levels of LDL are risk factors of preeclampsia in pregnant women.

High Serum Ratio of Soluble Fms-Like Tyrosine Kinase 1 (sFlt-1) to Placental Growth Factor (PIGF) and High Level of Low-Density Lipoprotein (LDL) as Risk Factors of Preeclampsia

Preeclampsia is an obstetric disease that is a health problem worldwide, including in Indonesia. Several studies have shown that changes in the maternal spiral arteries are thought to lead to preeclampsia. Preeclampsia in this decade has been associated with changes in angiogenesis regulatory proteins originating from the placenta and circulating in the mother's blood circulation, namely soluble FMS-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PlGF). The author was interested in examining the ratio of sFlt-1/PIGF and low-density lipoprotein (LDL) to the incidence of preeclampsia in pregnant women. This study used a case control analytic observational design. The research sample was selected by consecutive sampling of 20 cases and 20 controls. Univariate analysis was used to describe patient characteristics descriptively, and bivariate analysis was used to determine the relationship between the 2 variables There is no significant difference in the characteristics of the research subjects. Low PIGF levels are a risk factor for preeclampsia (OR 4.33; p 0.0302) with a cut-off value of 24.5. High sFlt-1 levels are a risk factor for preeclampsia (OR 4.33; p 0.027) with a cut-off value of 869.5. A high sFlt-1/PIGF ratio is a risk factor for preeclampsia (OR 4.33 p 0.030) with a cut-off value of 38. High LDL levels are a risk factor for preeclampsia (OR 6.0; p 0.013) with a cut-off value of 150 ,2. Low placental growth factor (PIGF), high levels of soluble FMS-like tyrosine kinase 1 (sFlt-1), and high levels of LDL are risk factors of preeclampsia in pregnant women.

Increased Expression Levels of Soluble Fms-Like Tyrosine Kinase-1 Inhibit the Development of the Nervous System

Introduction: Preeclampsia (PE) remains a leading cause of maternal and perinatal morbidity. At present, only limited options are available for the treatment of PE. Consequently, many patients need to terminate their pregnancies to relieve the disease. Soluble fms-like tyrosine kinase-1 (sFlt-1) is a decoy receptor of placental growth factor and vascular endothelial growth factor which can promote angiogenesis. Throughout pregnancy, the expression level of sFlt-1 continues to increase in both the mother with PE and her offspring. Material and Methods: In this experiment, we generated a zebrafish line expressing high levels of sFlt-1 and investigated changes in behavior and development of the nervous system. Results: At 96 h post-fertilization (hpf), the brain volume area of zebrafish in the experimental group (zFLT1+CasRx) was significantly smaller after injection than in the WT group (p < 0.05) and the negative control group (CasRx) (p < 0.05). At 96 hpf, compared with the WT group, the cerebral blood vessels in the CasRx control group and experimental group (zFLT1-sgRNA+CasRx) were significantly lower after injection (p < 0.05). Compared with the CasRx control group, the track movement distance and the mean track speed of zebrafish in the experimental group (zFLT1-sgRNA+CasRx) after the 6th injection were significantly decreased (p < 0.05). Conclusions: The increased expression levels of sFlt-1 in zebrafish inhibited the development of the cerebral blood vessels, influenced brain volumes, and inhibited behavioral activities. Our data suggest that the elevation of sFlt-1 in the pathological state of PE can inhibit the development of the nervous system in offspring.

MODULATION OF BIOMARKERS ASSOCIATED WITH LYMPHANGIOGENESIS AND CARDIOVASCULAR RISK BY POLYMORPHIC GENETIC VARIANTS OF AQUAPORINS AND HEPARANASE IN PSORIASIS

Objective: Psoriasis is a chronic inflammatory disease associated with cardiovascular risk factors. Aquaporins(AQP) are a family of channels, which can transport: water, urea, hydrogen peroxide and/or glycerol, essential for redox signalling and metabolic skin homeostasis. Heparanase(HPSE) is an endo--glucuronidase that cleaves heparan sulfate chains of proteoglycans from the extracellular matrix(ECM), an essential step in the neovascularization and cell growth process. Vascular endothelial growth factor-C(VEGF-C) is an important growth factor regulating lymphatic neovascularization and pathological processes associated with sodium accumulation in ECM in the skin. The VEGF soluble receptors(s-flt1) are decoy receptors present in endothelial cells, hematopoietic stem cells, monocytes, macrophages, and platelets. This study aims to evaluate the impact of AQP3, AQP7 and HPSE genetic polymorphisms in biomarkers related to cardiovascular risk in patients with psoriasis and their clinical severity determined by Psoriasis Area and Severity Index(PASI). Design and method: Sixty-three psoriasis patients with a mean age of 52.50 ± 12.81years. Sociodemographic, hemodynamic and routine blood laboratory data were collected. Biochemical parameters were determined in serum according to standardized methods. Genetic polymorphisms were determined by endpoint analysis and s-flt1 and VEGF-C by ELISA. Patients were stratified based on PASI:&lt; 5(G1) and &gt; or equal to 5(G2). For statistical analysis, SPSS program was used with a p-value &lt; 0.05. Results: Comparing the genotypic and allelic frequencies of the studied polymorphisms, no differences were found between G1 and G2. In general, patients with genotype AA of AQP3 had higher levels of s-flt1(p = 0.005) and VEGF-C(p = 0.048). For AQP7, genotype TT was associated with higher levels of mean platelet volume(p = 0.049) and lower levels of creatinine(Cr)(p = 0.023). Elevated levels of neutrophils(N)(p = 0.017) and potassium(p = 0.001) was observed in genotype AA of HPSE. For G1 was observed an increased level of: s-flt1(p = 0.022) and VEGF-C(p = 0.044) associated with genotype AA of AQP3; Cr in allele C of AQP7(p = 0.018), N in genotype CC of AQP7(p = 0.017). For G2 was observed: higher levels of leucocytes in allele C of AQP3(p = 0.016) and angiotensin-converting enzyme activity(ACE1) in allele T of AQP7(p = 0.033). Conclusions: AQP3, AQP7 and HPSE polymorphisms appear to modulate some biochemical parameters relevant to lymphangiogenesis associated with cardiovascular risk in a sample of patients with psoriasis.

Association of soluble Flt-1 with heart failure and cardiac morphology: The MESA angiogenesis study.

Soluble Fms-like tyrosine kinase 1 (sFlt-1) may inhibit angiogenesis. Higher levels of sFlt-1 are associated with worse prognosis in prevalent heart failure patients. The aim of this study was to better understand the role of sFlt-1 in heart failure pathogenesis by characterizing relationships between sFlt-1, cardiac morphology, and the composite outcome of incident heart failure or cardiovascular (CV) death in in a multiethnic cohort free of CV disease at baseline. sFlt-1 was measured in 1,381 participants in the Multi-Ethnic Study of Atherosclerosis Angiogenesis sub-study. Linear regression was used to estimate the association between sFlt-1 and cardiac morphology and Cox proportional hazard regression was used to estimate associations with incident heart failure or CV mortality. Over a median follow-up of 13.1 years, higher sFlt-1 levels were associated with incident heart failure or CV mortality independent from CV risk factors or NT-proBNP levels (HR 1.17, 95% CI 1.10-1.26, p < 0.001). Higher sFlt-1 levels were also associated with greater baseline left ventricular (LV) mass by cardiac MRI and increased loss of LV mass over the 10 years following the baseline exam (p-value 0.02 for each), but this association was no longer statistically significant after adjustment for baseline NT-proBNP (p=0.11 and 0.10 respectively). Baseline sFlt-1 levels are associated with incident heart failure and cardiovascular mortality independent of traditional CV risk factors or NT-proBNP. An association was also found with cardiac mass but was no longer significant after adjustment for NT-proBNP.

How Soluble Fms-Like Tyrosine Kinase 1 Could Contribute to Blood-Brain Barrier Dysfunction in Preeclampsia?

Preeclampsia is a pregnancy-related syndrome that courses with severe cerebrovascular complications if not properly managed. Findings from pre-clinical and clinical studies have proposed that the imbalance between pro- and anti-angiogenic factors exhibited in preeclampsia is a major component of its pathophysiology. In this regard, measurement of circulating levels of soluble tyrosine kinase-1 similar to fms (sFlt-1), a decoy receptor for vascular endothelial growth factor (VEGF), is a moderately reliable biomarker for the diagnosis of preeclampsia. However, few studies have established a mechanistic approach to determine how the high levels of sFlt-1 are responsible for the endothelial dysfunction, and even less is known about its effects at the blood-brain barrier (BBB). Since the expression pattern of VEGF receptors type 1 and 2 in brain endothelial cells differs from the observed in peripheral endothelial cells, and components of the neurovascular unit of the BBB provide paracrine secretion of VEGF, this compartmentalization of VEGF signaling could help to see in a different viewpoint the role of sFlt-1 in the development of endothelial dysfunction. In this article, we provide a hypothesis of how sFlt-1 could eventually be a protective factor for brain endothelial cells of the BBB under preeclampsia.

Preeclampsia at delivery is associated with lower serum vitamin D and higher antiangiogenic factors: a case control study

BackgroundPreeclampsia is characterized by decreased trophoblastic angiogenesis leading to abnormal invasion of spiral arteries, shallow implantation and resulting in compromised placentation with poor uteroplacental perfusion. Vitamin D plays an important role in pregnancy influencing implantation, angiogenesis and placental development. The objective of this study was to determine whether there is an association between serum vitamin D levels, and anti-angiogenic factors at the time of delivery and the occurrence of preeclampsia.MethodsThis nested case control study analyzed frozen serum samples at the time of delivery and related clinical data from women with singleton liveborn pregnancies who had participated in studies of the NICHD Stillbirth Collaborative Research Network. Women with a recorded finding of preeclampsia and who had received magnesium sulfate treatment prior to delivery were considered index cases (N = 56). Women without a finding of preeclampsia were controls (N = 341).ResultsWomen with preeclampsia had 14.5% lower serum vitamin D levels than women in the control group (16.5 ng/ml vs. 19 ng/ml, p = 0.014) with 64.5% higher sFlt-1 levels (11,600 pg/ml vs. 7050 pg/ml, p < 0.001) and greater than 2 times higher endoglin levels (18.6 ng/ml vs. 8.7 ng/ml, < 0.001). After controlling for gestational age at delivery and maternal BMI, vitamin D levels were 0.88 times lower (P = 0.051), while endoglin levels were 2.5 times higher and sFlt-1 levels were 2.1 times higher than in control pregnancies (P < 0.001).ConclusionsWomen with preeclampsia at time of delivery have higher maternal antiangiogenetic factors and may have lower maternal serum vitamin D levels. These findings may lead to a better understanding of the underlying etiology of preeclampsia as well as possible modifiable treatment options which could include assuring adequate levels of maternal serum vitamin D prior to pregnancy.

Mean arterial pressure for predicting preeclampsia in Asian women: a longitudinal cohort study

ObjectivePrevious studies suggested mean arterial pressure (MAP) had moderate predictive values in the first and second trimesters for the prediction of preeclampsia. However, the performance of MAP in Asian women...

SERUM LEVELS OF SOLUBLE FMS –LIKE TYROSINE KINASE -1 IN PRE-ECLAMPTIC AND ECLAMPTIC CASES AND ITS CORRELATION TO FETOMATERNAL OUTCOME

Preeclampsia is a multisystem progressive disorder characterized by the new onset of hypertension and proteinuria or the new onset of hypertension and significant end-organ dysfunction with or without proteinuria after 20 weeks of gestation or postpartum in previously normotensive women. It is develops due to placental and maternal vascular dysfunction and disappears after delivery gradually by time. The incidence is estimated to be between 3 and 10% of all pregnancies.Maternal endothelial dysfunction which leads to pre-eclamptic signs and symptoms is induced by high levels of the antiangiogenic factor sFLT1, which is produced in the placenta and released into the maternal circulation. sFLT1 is a soluble splice variant of the membrane-bound receptor VEGFR1 that binds to the proangiogenic proteins VEGF and placental growth factor (PlGF); therefore, sFLT1 acts as a ligand trap and antagonizes ligand-mediated angiogenic signalling via the cell surface receptors. Aim of the workThe aim of this work was to evaluate serum levels of soluble fms-like tyrosine kinase-1 (sFlt-1) in cases of severe preeclampsia and eclamptic fits,and to correlate serum levels of soluble fms-like tyrosine kinase-1 (sFlt-1) in these cases to outcome of fetus and mother and incidence of complication.

Increased Expression Levels of Soluble Fms-Like Tyrosine Kinase-1 Inhibits Nervous System Development of Zebrafish

Introduction Preeclampsia (PE) remains a leading cause of maternal and perinatal morbidity. At present, the treatments of preeclampsia are limited, and many patients need to terminate the pregnancy to relieve the disease. Soluble fms-like tyrosine kinase-1 (sFlt-1) is a decoy receptor of placental growth factor (PIGF) and vascular endothelial growth factor which can promote angiogenesis. Its level increases throughout pregnancy with preeclampsia and umbilical cord blood of their newborns. Material and methods In this experiment, we constructed zebrafish with high expression levels of sFlt-1 and explored their changes of nervous system developments and behaviors. Results Comparing with the WT group and the casRx group, the cerebral vascular developments at 72 h in the F1、F2 group were significantly decreased, the ratios of brain volume area to whole body area at 96 h were significantly decreased, and the behavioral trajectory distances and movement speeds at 6th day were shortened and slowed down. Conclusions The increased expression levels of sFlt-1 in zebrafish can inhibit the developments of cerebral blood vessels, brain volumes and the behavioral activities. It is speculated that elevated sFlt-1 in the pathological state of PE can inhibit the developments of nervous system in offspring.

Soluble Flt1 levels are associated with cardiac dysfunction in Black women with and without severe preeclampsia

ABSTRACT Background: We evaluate soluble fms-like tyrosine kinase-1 (sFlt-1) levels and cardiac function during pregnancy and postpartum among Black women with and without preeclampsia. Study design: Prospective longitudinal cohort study from 2015 to 2017 of Black women with preterm severe preeclampsia and normotensive pregnant controls.We obtained echocardiograms and sFlt-1 levels during pregnancy and postpartum. Results: 93 Black women were included (43 cases, 50 controls). Higher sFlt1 levels were correlated with worse longitudinal strain, diastolic dysfunction, decreased ventricular-arterial coupling, and increased chamber and arterial elastance at the time of preeclampsia diagnosis and postpartum. Conclusions: Higher sFlt1 levels are associated with cardiovascular dysfunction during pregnancy and postpartum.

Preeclampsia for the Nephrologist: Current Understanding in Diagnosis, Management, and Long-term Outcomes.

Preeclampsia is a multisystem progressive disorder of pregnancy that can be potentially catastrophic for the mother and the fetus. It involves complex perturbations of the kidney and systemic physiology, along with long-term effects on vascular and kidney health. Thus, the nephrologist plays a key role in the peripartum and long-term management of preeclampsia. Recent translational research has improved our understanding of its pathophysiology, and there is hope for novel therapies. In this review, we discuss the evolution of diagnostic criteria and dilemmas in the diagnosis of hypertensive disorders in pregnancy. We summarize the advances in the pathogenesis and prediction of preeclampsia. We describe the management and prevention of preeclampsia focusing specially on the forthcoming strategies from the nephrologist's perspective. We address the evidence regarding long-term outcomes for the mother and the child. We end with exploring areas warranting future research.

Association of serum angiogenic factors with bronchopulmonary dysplasia. The ANGIODYS cohort study.

Angiogenic factors may be involved in lung development. To evaluate the relations between maternal and cord blood angiogenic factors (sFlt-1, placental growth factor [PlGF], soluble endogline [sEng], transforming growth factor β [TGF-beta]) and their association with moderate and severe bronchopulmonary dysplasia (BPD) in very preterm growth-restricted infants. Prospective monocentric cohort study. Twenty-four mother-child dyads featuring antepartum preeclampsia, intra-uterine growth restriction (IUGR) and birth before 30 weeks' gestation were included. This ensured a 80% power to test whether sFlt-1 maternal levels would be twice as high in cases of BPD as in the absence of BPD. Four pro/anti-angiogenic factors from two pathways (sFlt-1, PlGF and sEng, TGF-beta) were measured in maternal serum before delivery (at the time of hospitalization or the day of birth) and in neonates' cord blood. Neonatal outcome was moderate to severe BPD, defined as oxygen requirement for at least 28 days and persistent need for oxygen or ventilatory support at 36 weeks' postmenstrual age. sFlt-1 levels were positively correlated in maternal serum and cord blood (rs = 0.83, p < .001) but levels of PlGF and TGF-beta and its receptor sEng were not. Among all the factors studied in cord and maternal blood, none was associated with BPD. In IUGR preterm babies born before 30 weeks' gestation from preeclamptic mothers, serum sFlt-1, PlGF and sEng, TGF-β levels were not correlated with BPD. The increased BPD risk in preterm neonates born from preeclamptic mothers cannot be related to high sFlt-1 levels.

Abnormal expression and clinical significance of 25-hydroxyvitamin D and sFlt-1 in patients with preeclampsia.

ObjectiveTo determine the association between levels of serum 25-hydroxyvitamin D (25[OH]D) and soluble fms-like tyrosine kinase 1 (sFlt-1) in patients with preeclampsia.MethodsClinical and demographic data were collected from patients with preeclampsia and healthy pregnant controls. Serum 25(OH)D and sFlt-1 levels were evaluated by enzyme-linked immunosorbent assay and their correlations were determined using Spearman’s rank correlation coefficient. Associations between serum 25(OH)D and sFlt-1 levels and disease severity and clinical parameters were evaluated.ResultsSignificantly lower serum 25(OH)D and higher sFlt-1 levels were observed in patients with preeclampsia (n = 100) versus controls (n = 100), and 25(OH)D was inversely correlated with sFlt-1 in patients with preeclampsia. Serum 25(OH)D levels were reduced, while sFlt-1 concentration was increased in patients with severe versus mild preeclampsia. Serum 25(OH)D levels were reduced in late-onset versus early-onset severe preeclampsia. Patients with preeclampsia who had lower serum 25(OH)D or elevated sFlt-1 levels showed significantly higher blood pressure indexes versus those with higher 25(OH)D or lower sFlt-1.ConclusionsLow serum 25(OH)D and high sFlt-1 may be candidate biomarkers for preeclampsia diagnosis and prognosis.