Blood Pressure In Preeclampsia Research Articles

Pulse Pressure as a Hemodynamic Parameter in Preeclampsia with Severe Features Accompanied by Fetal Growth Restriction.

Background: Modern management of preeclampsia can be optimized by tailoring the targeted treatment of hypertension to an individual's hemodynamic profile. Growing evidence suggests different phenotypes of preeclampsia, including those with a hyperdynamic profile and those complicated by uteroplacental insufficiency. Fetal growth restriction (FGR) is believed to be a result of uteroplacental insufficiency. There is a paucity of research examining the characteristics of patients with severe preeclampsia who do and who do not develop FGR. We aimed to elucidate which hemodynamic parameters differed between these two groups. Methods: All patients admitted to a single referral center with severe preeclampsia were identified. Patients were included if they had a live birth at 23 weeks of gestation or higher. Multiple gestations and pregnancies complicated by fetal congenital anomalies and/or HELLP syndrome were excluded. FGR was defined as a sonographic estimation of fetal weight (EFW) < 10th percentile or abdominal circumference (AC) < 10th percentile. Results: There were 76% significantly lower odds of overall pulse pressure upon admission for those with severe preeclampsia comorbid with FGR (aOR = 0.24, 95% CI = 0.07-0.83). Advanced gestational age on admission was associated with lower odds of severely abnormal labs and severely elevated diastolic blood pressure in preeclampsia also complicated by FGR. Conclusions: Subtypes of preeclampsia with and without FGR may be hemodynamically evaluated by assessing pulse pressure on admission.

Abstract 13744: The Association of Pre-Pregnancy Obesity on Postpartum Blood Pressure in Preeclampsia

Background: Women with preeclampsia have elevated risk of long-term cardiovascular disease, in part mediated by postpartum hypertension. Little is known about the association of pre-pregnancy obesity with postpartum blood pressure. Hypothesis: We hypothesized that women with pre-pregnancy obesity and preeclampsia will have higher postpartum blood pressure compared to women without preeclampsia. Methods: We included women with preeclampsia followed between 2021-2022 at a tertiary care academic center. An equal number of women without preeclampsia were then included, matched for body mass index (BMI). Pre-pregnancy weight (exposure variable) was categorized according to BMI (in kg/m 2 ) at the initial antenatal visit as follows: normal weight (&lt;25), overweight (25-&lt;30), class I obesity (30-&lt;35) and class II+ obesity ( &gt; 35 kg/m 2 ). MAP from the 6 week postpartum visit was the outcome variable. Adjusted linear regression was performed for the association of BMI category with MAP, stratified by preeclampsia status. Interaction between BMI category and preeclampsia on the outcome of MAP was tested in the fully adjusted model. Results: Among 426 women, 247 had preeclampsia. Mean age was 31 + 6 and 32 + 5 years for women with and without preeclampsia, respectively. 54% of women with preeclampsia and 43% without identified as Black. Chronic hypertension was present in 30% vs 11% of women with vs without preeclampsia. Among women with preeclampsia, obesity class II/III was associated with higher postpartum MAP than normal weight (Table). This association was not seen in women without preeclampsia (p-value interaction = 0.004). Conclusion: Higher pre-pregnancy BMI is associated with greater postpartum MAP in women with preeclampsia, but not in women without preeclampsia. These findings underscore the importance of reducing the burden of pre-pregnancy obesity in populations at risk for preeclampsia, to prevent long-term adverse cardiovascular outcomes after pregnancy.

Abstract 15468: Cd81 Interacts With Sodium Chloride Cotransporter in Lps-Induced Preeclampsia Rats and in Cultured Mouse Renal Distal Convoluted Tubule Cells

Kidney regulates blood pressure mainly through salt/water reabsorption affected by sodium transport proteins along nephron. We have reported that placental CD81 plays an important role in the pathogenesis of preelampsia. In order to explore the connection between CD81 and renal sodium transport proteins in preelampsia, we studied their interactions in vivo and in vitro. On the gestation day 18 of lipopolysaccharide-induced preeclamsia model rats with hypertension and albuminuria, the renal protein abundances of NKCC2 (150±14,% of control, n=5-6/group, mean±SE, t-test, same as below), p-NKCC2(567±70%), NCC (254±41) and WNK4 (196±12) were increased together with an increase of CD81 in kidney (225±46) and urinary exosomes(396±100). Renal NCC (215±30) was elevated while NKCC2 tended to increase at 17000g pellet in LPS group. There was no change of both NKCC2 and NCC at 200,000g pellet. In kidney homogenates, CD81 was coimmunoprecipitated with NKCC2, NCC, not NHE3 while NKCC2, NCC were coimmunoprecipitated with CD81 not CD63. In renal plasma-membrane-enriched fraction NCC, not NKCC2, was also increased in preeclampsia rats. In the apical membrane of renal tubules CD81 was colocalized with NCC while minimum colocalization was found between CD81 and NKCC2. In cultured mouse distal convoluted tubule cells, CD81 was colocalized with NCC while CD81 deletion with siRNA decreased NCC and partially reversed lipopolysaccharide-induced increase of NCC. Furthermore, CD81 was detected only in the urinary exosomes from preeclampsia patients along with increases in NKCC2 (6063±811) and NCC(1085±191)relative to normal pregnant women (n=6/group, t-test). Those findings suggest that CD81 interacts with renal NCC in vivo and in vitro and the increase of renal CD81 may up-regulate NCC, possibly NKCC2 as well, and contribute to the increased blood pressure in preeclampsia.

Association of serum soluble endoglin with preeclampsia

Objectives: To determine and compare the serum soluble Endoglin (sEng) levels among pregnant women with preeclampsia (PE) and women having normal pregnancy. Methodology: This cross-sectional study was carried at IBMS KMU and the data collection was carried out in the department of Gynecology &amp; obstetrics, Lady Reading hospital, Peshawar, from June 2019 to July 2020. A total of 138 pregnant women at the gestational age of 26-30 weeks were included. The study sample was divided into two groups. Group A: Pre-Eclamptic (n=92). Group B: Normotensive Control Group; women with normal pregnancy (n=46). Results: Mean age in PE group was considerably lower as compared to control group (p&lt;0.001). Similarly, mean age at the time of marriage was significantly lower in the PE group compared to control group (19.40±1.92 vs 21.17±2.19 years, p&lt;0.001). Both mean systolic and diastolic blood pressure in PE and control group was noted to be significantly differed (169.78 ± 16.64/ 114.62 ± 9.34 vs 119.57 ± 1.07/ 78.48 ± 5.56 mm Hg, p&lt;0.05). PE group had statistically significantly higher sEng levels compared to control group (13.42 ± 2.94vs3.47 ± 2.80 ng /ml, p &lt;0.001).

Neutrophil gelatinase-associated lipocalin and Endothelin-1 as markers for the onset and severity of preeclampsia

Background: The onset of preeclampsia (PE) may be early (EOPE), or late (LOPE). Preeclampsia may also be characterized by severe features (PS) or without severe features (PNS). This study aimed to predict the onset and severity of PE using biomarkers including neutrophil gelatinase-associated lipocalin (sNGAL) and endothelin-1 (ET-1). Method: This was a case-control study from January to June 2020. The study involved 270 pregnant women (control=135, PE=135), aged between 18-37 years. The cases and controls were matched by maternal and gestational age at sampling. Serum samples were assayed for sNGAL and ET-1 using the ELISA technique. Results: Serum NGAL and ET-1 were significantly increased in PE and also increased in PE characterized by severe features (P&lt;0.010). Both sNGAL and ET-1 positively correlated with blood pressure in PE (P&lt;0.050). In predicting PE, the area under the curve, sensitivity and specificity of sNGAL were 0.76, 46.2% and 97.8% while that of ET-1 were 0.82, 66.8%, and 92.5% respectively. Also, ET-1 could differentiate PS from PNS with a sensitivity of 85.7% and specificity of 82.1%. Conclusion: Serum ET-1 is better than sNGAL in the prediction of PE. We recommend screening pregnant women using ET-1 for the early detection and management of PE.

Hypertension: Potential Player in Cardiovascular Disease Incidence in Preeclampsia.

Preeclampsia (PE) is one of the complications, that threatens pregnant mothers during pregnancy. According to studies, it accounts for 3-7% of all pregnancies, and also is effective in preterm delivery. PE is the third leading cause of death in pregnant women. High blood pressure in PE can increase the risk of developing cardiovascular disease (CVD) in cited individuals, and is one of the leading causes of death in PE individuals. Atrial natriuretic peptide (ANP), Renin-Angiotensin system and nitric oxide (NO) are some of involved factors in regulating blood pressure. Therefore, by identifying the signaling pathways, that are used by these molecules to regulate and modulate blood pressure, appropriate treatment strategies can be provided to reduce blood pressure through target therapy in PE individuals; consequently, it can reduce CVD risk and mortality.

NON-PHARMACHOLOGICAL THERAPY IN DECREASING BLOOD PRESSURE AMONG PREGNANT WOMEN: LITERATURE REVIEW

Pregnancy in which the body of a pregnant woman undergoes physical changes, and psychological changes due to increased pregnancy hormones. Hormonal changes during pregnancy cause changes in the cardiovascular system with increased blood pressure in pregnant women and triggers preeclampsia in pregnancy. The purpose of the literature study was to identify several non-pharmacological therapies in reducing blood pressure in pregnant women with preeclampsia. The research method used is a literature study with a narrative review approach. Search data using databases such as PubMed, EBSCO, and Google Scholar. The keywords used were “hypertension”, “non-pharmachological therapies”, “preeclampsia”, “pregnancy”. There were 7 articles that discussed non-pharmacological therapy by means of aerobic exercise, foot massage, progressive muscle relaxation and breathing control techniques, autogenic training, hydrotherapy, mushroom diet, cognitive behavioral therapy. Non-pharmacological therapy by reducing blood pressure in preeclampsia in pregnant women affects systolic and diastolic blood pressure during the therapy program with a period of time and a relaxation phase. In addition, other therapies reduce arterial stiffness in pregnant women with chronic hypertension.

Role of circulatory Telomere length, Oxidative stress markers, and inflammatory markers with Increasing Blood pressure in PREECLAMPSIA - A Study in western Uttar Pradesh, India

Role of circulatory Telomere length, Oxidative stress markers, and inflammatory markers with Increasing Blood pressure in PREECLAMPSIA - A Study in western Uttar Pradesh, India

17-OHPC reduces blood pressure, markers of inflammation and prolongs time to delivery during preeclampsia

Preeclampsia (PE), new onset hypertension during pregnancy, is a progesterone deficient state and is associated with an imbalance among CD4+ T cells, natural killer (NK) cells, and inflammatory cytokines. Progesterone induces progesterone induced blocking factor (PIBF) which stimulates IL-4/T helper 2 cells (TH2) as mechanisms to quell inflammation. UMMC PE patients have significantly lower progesterone compared to normotensive pregnant women (NP).This study was designed to test the hypothesis that progesterone, in the form of 17-hydroxyprogesterone caproate (17-OHPC), stimulates PIBF/IL-4/TH2, as a mechanism of reducing NK/TH1s and improves blood pressure in PE.

Relationship between Elevated Maternal Serum Podocalyxin Concentrations with Blood Pressure Values and Routine Laboratory Parameters in Preeclampsia

Summary Podocalyxin (PCX) is a glycoprotein member of the CD34 transmembrane sialomucin family and covers the surface of podocytes. It is assumed to be a marker of glomerular endothelial injury. In conditions, podocalyxin excretion in the urine is increased as a result of podocyte injury. Recent studies show that PCX is expressed not only in kidneys but also in the endothelial cells of other organs. Preeclampsia (PE) is characterized by new-onset hypertension, generalized endothelial injury, and glomerular alteration. Having this in mind, in the present study, we aimed to: (1) determine circulating PCX levels in sera of women with preeclampsia and normal pregnancy; (2) explore for an association between PCX and blood pressure and (3) investigate a possible relationship between PCX and routine laboratory markers of cardiac and renal injury/dysfunction. Fifty-five women with preeclampsia were examined. The mean age of patients was 24.9±6 years, and the mean age of the control group of 35 women with normal pregnancies was 24.7±5.4 years. The enzyme-linked immunosorbent assay (ELISA) was used to determine concentrations of PCX. Levels of serum PCX in preeclamptic women were statistically significantly higher than those in women with normal pregnancy: 2.66±0.67 vs. 2.40±0.33 ng/ml (p=0.03). Podocalyxin correlated with SBP (r=0.30; p=0.004), DBP (r=0.35; p=0.0007), uric acid (r=0.32; p=0.002), CPK (r=0.22; 0.03) and its isoenzyme CK-MB (r=0.21; p=0.04). Our results showed significantly higher levels of serum PCX in women with preeclampsia than in healthy pregnancy. Elevated podocalyxin levels are associated with an increase in blood pressure in preeclampsia. We found a relationship between PCX and routine laboratory indicators of cardiac (CPK and CK-MB) and renal injury/dysfunction (uric acid). PCX has the potential as a future preeclampsia diagnostic biomarker.

Placental Ischemia Says “NO” to Proper NOS-Mediated Control of Vascular Tone and Blood Pressure in Preeclampsia

In this review, we first provide a brief overview of the nitric oxide synthase (NOS) isoforms and biochemistry. This is followed by describing what is known about NOS-mediated blood pressure control during normal pregnancy. Circulating nitric oxide (NO) bioavailability has been assessed by measuring its metabolites, nitrite (NO2) and/or nitrate (NO3), and shown to rise throughout normal pregnancy in humans and rats and decline postpartum. In contrast, placental malperfusion/ischemia leads to systemic reductions in NO bioavailability leading to maternal endothelial and vascular dysfunction with subsequent development of hypertension in PE. We end this article by describing emergent risk factors for placental malperfusion and ischemic disease and discussing strategies to target the NOS system therapeutically to increase NO bioavailability in preeclamptic patients. Throughout this discussion, we highlight the critical importance that experimental animal studies have played in our current understanding of NOS biology in normal pregnancy and their use in finding novel ways to preserve this signaling pathway to prevent the development, treat symptoms, or reduce the severity of PE.

Correlation between Serum Inflammatory and Oxidative Stress Markers with Blood Pressure in Preeclampsia

Correlation between Serum Inflammatory and Oxidative Stress Markers with Blood Pressure in Preeclampsia

Comparison of the effects on maternal endothelial cell activation: an in vitro study of anti-hypertensive drugs clinically used in pre-eclampsia.

Endothelial cell dysfunction in pregnancy, which can be induced by placental factors, is the fundamental component of the pathogenesis of pre-eclampsia. The dysfunctional vascular endothelium disrupts the balance of vasodilatory and vasoconstrictive factors, resulting in increasing blood pressure. There is currently no effective treatment for pre-eclampsia and effective control of hypertension may reduce neonatal morbidity and mortality by prolonging gestation, especially in cases of early onset disease. To date methyldopa, labetalol, nifedipine and metoprolol are recommended for controlling blood pressure in pre-eclampsia. All of these drugs have different mechanisms of action. In this in vitro study we investigated whether different types of anti-hypertensive drugs could have different effects on improving maternal endothelial cell dysfunction. Endothelial cells (HMEC-1) were exposed to phorbol-12-myristate-13-acetate (PMA) or pre-eclamptic sera or extracellular vesicles (EVs) derived from pre-eclamptic placentae, in the presence of each of the studied anti-hypertensive drugs (methyldopa, labetalol, nifedipine and metoprolol) or placebo for 24 h. Endothelial cell-surface adhesion molecule (ICAM-1) and monocyte adhesion were measured. The expression of cell-face ICAM-1 by HMEC-1 cells and THP-1 monocyte adherent to HMEC-1 that were exposed to three separate well-known activators of endothelial cells in the presence of four anti-hypertensive drugs was significantly reduced regardless of the dose. However, the effect on the reduction of ICAM-1 expression and monocyte adhesion was not significantly different between the four medications. Our data suggest that the beneficial effect on improving endothelial cell function by these commonly prescribed anti-hypertensive drugs is seemingly independent of the anti-hypertensive mechanisms of the medication.

A study of the association between angiotensinogen (AGT) gene polymorphism (M235T) and preeclampsia in Thai pregnant women

AGT M235T gene polymorphism may cause increased blood pressure in preeclampsia in pregnancy; however, the evidence remains controversial. This study investigated the association between AGT M235T and preeclampsia in Thai pregnant women. A case-control study was conducted to compare the distributions of AGT M235T genotypes and alleles between 142 normotensive pregnancies as controls and 61 preeclampsia pregnancies as cases in a tertiary-care university hospital in Chiang Mai, Thailand. The results show that the distribution of AGT M235T genotypes (MM, MT and TT) of both groups were not significantly different (preeclampsia: 0.0, 16.4, 83.6%; control: 2.1, 22.5, 75.4%, respectively; p = .30). Additionally, there was no statistical difference in the distribution of AGT M235T alleles (M and T alleles) (preeclampsia: 8.2 and 91.8% versus control: 13.4 and 86.6%, respectively; p = .14). In this study, the distributions of AGT M235T were not different in both groups. Therefore, AGT M235T polymorphism may not play a significant role in preeclampsia pathophysiology in Thai population. Impact statement What is already known on this subject? Preeclampsia is one of the major complications during pregnancy; it significantly affects maternal and perinatal morbidity and mortality. Effort has been made to find markers and predictors that are associated with the pathophysiology of preeclampsia. AGT M235T gene polymorphism may cause increased blood pressure in preeclampsia pregnancy; however, evidences are still controversial. What do the results of this study add? We conducted a case-control study to compare the distributions of AGT M235T genotypes and alleles between 142 normotensive pregnancies as controls and 61 preeclampsia pregnancies as cases. The results show that preeclamptic women are more likely to deliver at an earlier gestational age and have a smaller baby in comparison with the normotensive group. In addition, women with preeclampsia had a higher chance of having an operative delivery and caesarean section. However, the distribution of AGT M235T polymorphism of preeclampsia women and the control group were not significantly different. What are the implications of these findings for clinical practice and/or further research? AGT M235T polymorphism may not play a significant role in preeclampsia pathophysiology in Thai population.

Prophylactic Iron Supplementation in Pregnancy and its Implications in Development of Pre-eclampsia: A Case-control Study

Introduction: Pre-eclampsia is a serious complication of pregnancy and is associated with increased maternal and perinatal morbidity and mortality. Increased iron and ferritin concentration is associated to a higher risk of pre-eclampsia and prophylactic iron supplementation can sometimes be harmful to pregnant women who are otherwise not iron deficient. Aim: To analyse serum iron, serum ferritin, serum Transferrin Receptor (sTFR) levels, Total Iron Binding Capacity (TIBC) among iron supplemented pre-eclamptic cases and normotensive pregnant controls. Materials and Methods: This prospective, observational, case- control study was conducted in Jaipur National University Institute of Medical Sciences and Research Centre (JNUIMSRC), Jaipur, Rajasthan, India for a period of one year from (February 2019-January 2020). A total of 200 pregnant females, all on iron supplementation during the course of their pregnancy, 100 in pre-eclampsia group (case group); 100 in normotensive group (control group), in third trimester and between 18- 45 years of age were enrolled in the study. Serum iron, serum ferritin, sTFR and TIBC were estimated using fully automated analysers. Results: Median Interquartile Range (IQR) of serum ferritin levels in cases were higher than the controls [41 (30-70) vs 24 (17-44); p&lt;0.001]. Serum ferritin in cases were also found to correlate positively with systolic (r=0.37, p=0.001) Blood Pressure (BP) whereas TIBC correlated negatively with diastolic BP (r=-0.238, p-value=0.017). The median IQR differences of TIBC values among cases and controls were insignificant {485 (404-523) vs 493 (448- 544)} and differences of median IQR of sTFR values among cases and controls were significant {8.5 (7-9) vs 8.9 (8-10)}. Subjects with serum feritin levels &gt;40 ng/mL had three times increased risk of PE (Odds ratio=3, 95% Cl=1.571-5.157). Conclusion: Elevated serum ferritin, decreased sTFR levels and correlation of Ferritin and TIBC to BP in pre-eclampsia compels us to put cautionary remarks over testing these parameters before continuing with iron supplements. This may prevent a possible iron related added complications in pre-eclampsia and help clinicians decide about restricting/lowering iron supplement doses in case a situation of iron overload arise.

Effects of statins on preeclampsia: A systematic review.

Preeclampsia is a serious complication of pregnancy which increases the morbidity and mortality of both the fetus and pregnant woman. It is characterized by imbalances in angiogenesis, inflammation and endothelial dysfunction which cause the development of hypertension and proteinuria, sometimes progressing into a multisystem disorder. The aim of this systematic review was to analyze all the available data on statins and preeclampsia. MEDLINE/PubMed, OVID, EMBASE, Web of Sciences, and SCOPUS were searched from inception to May 5, 2020. Any study evaluating the effects of statins on women with preeclampsia or HELLP syndrome or who were at risk for it has been included as well as the studies on the placenta of preeclamptic women. 12 articles which included 136 pregnant women and 35 placental samples from hypertensive and normotensive women were analyzed. They showed contradictory effects of statins on blood pressure in preeclampsia, on soluble FMS-like tyrosine kinase-1 (sFlt-1) as well as soluble endoglin (sEng). However, statins caused a significant dose-dependent reduction of sFlt-1 secretion from isolated cytotrophoblasts and an increased secretion of sEng (at least in some studies) in primary HUVECs and placental explants obtained from patients with preeclampsia. Statins also increased eNOS in preeclamptic placentas. Statins were beneficial for patients with antiphospholipid syndrome (APS) preventing preeclampsia and it seems that they might prevent complications of HELLP. It seems that statins might be beneficial for preventing or treating preeclampsia. Nevertheless, further studies are needed to provide definitive conclusions regarding these effects of statins.

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.

Differences of Cardiovascular Risk-based on Atherogenic Index Plasma Dan Framingham Risk Score in Postpartum with Preeclampsia and Normotensive

BACKGROUND: Cardiovascular disease is the number one cause of death in women worldwide. Preeclampsia may be more than just risk factor for the development of cardiovascular disease later in life. Systematic reviews suggested approximately double the risk of ischemic heart disease, cerebrovascular incidents, and mortality of cardiovascular disease after preeclampsia.&#x0D; AIM: The aim of the study was to analyze the differences of cardiovascular risk later in life-based on atherogenic index plasma and Framingham risk score (FRS) in postpartum women with preeclampsia compared with normotensive women.&#x0D; METHODS: This is study a comparative analytic study with case–control design on 46 subjects, divided by 23 postpartum preeclampsia patients as a case sample subject and 23 postpartum with no history of hypertension as the control group. Subjects were examined for blood pressure, height, weight, and asked to fast for at least 8 h before blood lipid profile and glucose were examined with laboratory methods. Atherogenic index plasma and FRS were measured. Data were analyzed using SPSS version 25. p &lt; 0.05 was considered significant.&#x0D; RESULTS: Based on the results, the study found significant differences between systolic and diastolic blood pressure in preeclampsia compared to the control group. Median systolic and diastolic blood pressure in the preeclampsia group compared to control group were 180 versus 110 in systolic blood pressure; 100 versus 80 in diastolic blood pressure with p &lt; 0.000. Total cholesterol, low-density lipid, high-density lipoprotein, and triglycerides levels in preeclampsia were 218.38 ± 23.26 mg/dL, 128.60 ± 22.74 mg/dL, 38.60 ± 5.99 mg/dL, and 252.73 ± 47.16 mg/dL, respectively, with p &lt; 0.05 and non-preeclampsia group were 143.0 ± 16.82 mg/dL, 69.17 ± 23.03 mg/dL, 51.73 ± 8.65 mg/dL, and 121.30 ± 14.65 mg/dL, respectively, with p &lt; 0.05. Differences in plasma atherogenic index values can clearly be observed in the preeclampsia and control groups (p &lt; 0.05). A similar interpretation was found in the FRS (p &lt; 0.05). There was a significant positive correlation between age and body mass index with atherogenic index plasma and FRS in preeclamptic group.&#x0D; CONCLUSION: There was a significant difference in atherogenic index plasma and Framingham risk score of postpartum preeclampsia and normotensive women.

A comparative study of Copper/zinc ratio and Systolic Blood Pressure in Preeclampsia

A comparative study of Copper/zinc ratio and Systolic Blood Pressure in Preeclampsia

Abstract P3047: Soluble Guanylyl Cyclase Stimulators And Activators Inhibit Hypoxia-induced Placental Sflt-1 Levels

Preeclampsia (PE) is a pregnancy-specific disease characterized by placental ischemia, maternal endothelial dysfunction, and hypertension. The ischemic placenta releases anti-angiogenic factors, such as sFlt-1, which antagonizes the angiogenic factors, Placental Growth Factor (PlGF) and Vascular Endothelial Growth Factor (VEGF), causing endothelial dysfunction and impaired nitric oxide (NO) signaling. During normal pregnancy, NO would bind soluble guanylyl cyclase (sGC) increasing cGMP levels leading to vasodilation. However, in PE this signaling is reduced. sGC stimulators and activators are a novel class of drug that directly stimulate sGC despite low levels of NO. Our preliminary data suggest that sGC modulators reduce hypertension in an animal model of PE, but the mechanisms are not known. Therefore, this study tested the hypothesis that sGC stimulators (Riociguat) and activators (Cinaciguat) attenuate sFlt-1 production and increase PlGF levels in the placenta. Placentas were obtained from normal pregnant rats on gestational day 19. Isolated placental villi were plated (1 per well) and coated with Matrix Matrigel Basement Membrane. The villi were treated with various doses of sGC modulators (0.2μM, 1μM, 10μM, 30μM) and then exposed to a hypoxic environment (1% oxygen) for 48 hours. Levels of sFlt-1, PlGF, and VEGF were determined using an Enzyme-Linked Immunosorbent Assay kit.sFlt-1 concentration was significantly reduced in both groups treated with the stimulator or activator compared to the untreated group. The greatest attenuation was observed with the 30μM sGC activator treatment (Untreated, 5117±1313 pg/mL; 30μM sGC stimulator, 3975±621pg/mL, 30μM sGC activator, 3811±712 pg/mL, P&lt;0.05). PlGF was not significantly different between groups, however, VEGF concentrations were significantly increased at higher doses (Untreated, 3099±100 pg/mL; 30μM sGC stimulator, 3871±449 pg/mL 30μM sGC activator, 3952±252 pg/mL; p&lt;0.05). These data suggest that sGC modulators significantly attenuate sFlt-1 and thus, improve the sFlt-1/PlGF and sFlt-1/VEGF ratios. Therefore, a potential mechanism whereby sGC modulators reduce blood pressure in PE is by inhibiting hypoxia-induced placental sFlt-1 levels.