Citrullination preeclampsia

BACKGROUND: Observational studies have revealed that metabolic disorders are closely related to the development of preeclampsia (PE). However, there is still a research gap on the causal role of metabolites in promoting or preventing PE. We aimed to systematically explore the causal association between circulating metabolites and PE. METHODS: Single nucleotide polymorphisms (SNPs) from genome-wide association study (GWAS) of 486 blood metabolites (7,824 participants) were extracted as instrumental variables (P < 1 × 10- 5 ), GWAS summary statistics for PE were obtained from FinnGen consortium (7,212 cases and 194,266 controls) as outcome, and a two-sample Mendelian randomization (MR) analysis was conducted...

AIM: To develop prognostic models for arterial hypertension (AH) and atherosclerosis based on studying the totality and significance of traditional and disease-mediated risk factors (RFs) in women with rheumatoid arthritis (RA). MATERIAL AND METHODS: 223 female patients with RA aged 54.9±2.1 years were evaluated at the premises of the polyclinic of the Gulla Municipal Hospital #4 (Barnaul), the "Health Center", the City Rheumatology Department of the polyclinic, and the Hospital Department in 2016-2019...

In preeclampsia, the shallow invasion of cytotrophoblast cells to uterine spiral arteries, leading to a reduction in placental blood flow, is associated with an imbalance of proangiogenic/antiangiogenic factors to impaired nitric oxide (NO) production. Proangiogenic factors, such as vascular endothelial growth factor (VEGF) and placental growth factor (PlGF), require NO to induce angiogenesis through antioxidant regulation mechanisms. At the same time, there are increases in antiangiogenic factors in preeclampsia, such as soluble fms-like tyrosine kinase type 1 receptor (sFIt1) and toll-like receptor 9 (TLR9), which are mechanism derivates in the reduction of NO bioavailability and oxidative stress in placenta...

Preeclampsia (PE), presenting with onset hypertension and proteinuria, is a pregnancy-specific disorder that can result in maternal and fetal morbidity and mortality. Insufficient trophoblast invasion and migration has been considered to be an important cause of this disease. The present study aimed to investigate the role of peptidyl arginine deiminase 4 (PAD4), whose knockdown has been previously indicated to reduce inflammation and susceptibility to pregnancy loss in mice, in the development of PE in vitro ...

BACKGROUND AND PURPOSE: Preeclampsia, characterized by hypertension, proteinuria and restriction of fetal growth, is one of the leading causes of maternal and perinatal mortality. So far, there is no effective pharmacological therapy for preeclampsia. The present study was conducted to investigate the effects of supplementation with l-citrulline in Dahl salt-sensitive rats, a model of superimposed preeclampsia. EXPERIMENTAL APPROACH: Parental Dahl salt-sensitive rats were treated with l-citrulline (2...

Preeclampsia is a spontaneously occurring pregnancy complication diagnosed by new-onset hypertension and end-organ dysfunction with or without proteinuria. This pregnancy-specific syndrome contributes to maternal morbidity and mortality and can have detrimental effects on fetal outcomes. Preeclampsia is also linked to increased risk of maternal cardiovascular disease throughout life. Despite intense investigation of this disorder, few treatment options are available. The aim of this study was to investigate the potential therapeutic effects of maternal l-citrulline supplementation on pregnancy-specific vascular dysfunction in the male C57BL/6J × female C57BL/6J C1q -/- preeclampsia-like mouse model...

Supplemental arginine has shown promise as a safe therapeutic option to improve endogenous nitric oxide (NO) regulation in cardiovascular diseases associated with endothelial dysfunction. In clinical studies in adults, L-arginine, an endogenous amino acid, was reported to improve cardiovascular function in hypertension, pulmonary hypertension, preeclampsia, angina, and MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) syndrome. L-citrulline, a natural precursor of L-arginine, is more bioavailable than L-arginine because it avoids hepatic first-pass metabolism and has a longer circulation time...

BACKGROUND: Pravastatin, a known inducer of endothelial nitric-oxide synthase (eNOS) was demonstrated in human placenta, however the exact mechanism of it's action is not fully understood. Since placental NO (nitric oxide) synthesis is of primary importance in the regulation of placental blood flow, we aimed to clarify the effects of pravastatin on healthy (n = 6) and preeclamptic (n = 6) placentas (Caucasian participants). METHODS: The eNOS activity of human placental microsomes was determined by the conversion rate of C14 L-arginine into C14 L-citrulline with or without pravastatin and Geldanamycin...

Preeclampsia, a serious multisystem disorder specific to human pregnancy, remains a considerable burden of disease worldwide. Reduced nitric oxide bioavailability is proved to be crucial in the maternal and fetal pathophysiology of preeclampsia. G-protein-coupled Receptor Kinase Interactor-1 (GIT1) is a novel endothelial nitric oxide synthases (eNOS) interactor mediator. The aim of this paper is to investigate the effect of GIT1 on preeclampsia. Blood pressure (BP) was measured using a carotid catheter-calibrated eight-chamber tail-cuff system (CODA) at the same time daily...

The primary driving force in preeclampsia (PE) appears to be excessive secretion of fms-like tyrosine kinase-1 (sFlt-1), a truncated decoy receptor for vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) that induces systemic endotheliopathy by depriving endothelial cells of the trophic support conferred by VEGF. Factors which boost placental sFlt-1 production in PE include hypoxia - reflecting improper placentation - oxidative stress, and deficient production of hydrogen sulfide (H2S)...

Gestational diabetes mellitus (GDM) is a unique form of glucose intolerance, in that it is transient and solely occurs in pregnancy. Pregnancies with GDM are at high risk of developing preeclampsia (PE), a leading cause of fetal and maternal morbidity or mortality. Since PE is associated with excessive activation of circulatory neutrophils and occurrence of neutrophil extracellular traps (NETs) in affected placentae, we examined these features in cases with GDM, as this could be a feature linking the two conditions...

OBJECTIVE: To evaluate early-pregnancy levels of ADMA (asymmetric dimethylarginine) in recurrent hypertensive pregnancy. STUDY DESIGN: In this retrospective observational study, blood samples from 35 normotensive women with a previous hypertensive pregnancy were obtained preconceptionally and at 12, 16 and 20weeks in their next pregnancy. We assessed ADMA, symmetric dimethylarginine (SDMA), l-arginine and l-citrulline. We analyzed differences in longitudinal patterns between normotensive (NT, n=18) and recurrent hypertensive (HT, n=17) pregnancies by linear mixed models, with a sub-analysis for preeclampsia (PE, n=6)...

Endogenously produced inhibitors of nitric oxide (NO) synthase, in particular asymmetric dimethylarginine (ADMA), are currently considered of importance in various disease states characterized by reduced NO availability. We investigated the association between plasma levels of ADMA, symmetric dimethylarginine (SDMA), L-arginine, and citrulline and perinatal factors and outcome in 130 preterm (gestational age ≤ 30 weeks) very low birth weight (VLBW, < 1500 g) infants. Plasma samples were collected 6-12 h after birth...

Excessive or aberrant generation of neutrophil extracellular traps (NETs) has recently become implicated in the underlying aetiology of a number of human pathologies including preeclampsia, systemic lupus erythromatosus, rheumatoid arthritis, auto-antibody induced small vessel vasculitis, coagulopathies such as deep vein thrombosis or pulmonary complications. These results imply that effective pharmacological therapeutic strategies will need to be developed to counter overt NETosis in these and other inflammatory disorders...

Preeclampsia is a syndrome characterized by hypertension and proteinuria. The aim of this study is to find the relationship between preeclampsia, asymmetric dimethyl arginine (ADMA), and the oxidant/antioxidant system. Twenty-one preeclamptic and 28 normal pregnant women were included in this study. In cord bloods, ADMA and oxidant/antioxidant parameters were measured. Asymmetric dimethyl arginine levels were significantly increased in preeclamptic pregnancies compared to the control group (p = 0.006). The activities of antioxidant enzymes and malondialdehyde levels were increased in the preeclamptic group compared to the control group (p < 0...

Preeclampsia, a pregnancy-specific syndrome characterized by hypertension, proteinuria and edema, is a major cause of fetal and maternal morbidity and mortality especially in developing countries. Bj-PRO-10c, a proline-rich peptide isolated from Bothrops jararaca venom, has been attributed with potent anti-hypertensive effects. Recently, we have shown that Bj-PRO-10c-induced anti-hypertensive actions involved NO production in spontaneous hypertensive rats. Using in vitro studies we now show that Bj-PRO-10c was able to increase NO production in human umbilical vein endothelial cells from hypertensive pregnant women (HUVEC-PE) to levels observed in HUVEC of normotensive women...

BACKGROUND/OBJECTIVES: Nitric oxide (NO) has been proposed as a mediator of vascular expansion during pregnancy. Inability to increase NO synthesis and/or production of its precursor, arginine, may be a contributor to pregnancy-induced hypertension or preeclampsia. Because maternal weight is associated with blood pressure and risk of preeclampsia during pregnancy, it may also influence arginine and/or NO production. The purpose of this study was to determine the in vivo arginine production and NO synthesis rate in pregnant women with normal (n=10) and low (n=10) body mass indices (BMIs)...

Nitric oxide is produced enzymatically by the nitric oxide synthase (NOS), which converts L-arginine in the presence of oxygen to L-citrulline and NO. Moreover, it has been reported that asymmetric dimethylarginine (ADMA) acts as is an endogenous inhibitor of endothelial NOS (eNOS) by competing with the enzyme for L-arginine. In this study, we measured L-arginine and ADMA in normal and preeclamptic women, and also investigated the association between the Glu298Asp eNOS gene polymorphism and preeclampsia. Finally, we assessed eNOS expression levels in the placentas of both normal and preeclamptic patients, using Western blot and immunohistochemistry...

BACKGROUND: Several lines of evidence point to the dysfunction of the endothelial l-arginine-NO system in preeclampsia. We investigated the influence of dietary supplementation with l-arginine on blood pressure and biochemical measures of NO production in women with preeclampsia in prospective, randomized, placebo-controlled study. DESIGN: The 61 preeclamptic women on a standardized low nitrate diet received orally 3 g of l-arginine (n = 30) or placebo (n = 31) daily for 3 weeks as a supplement to standard therapy...

AIMS: Umbilical blood vessels are not innervated and regulation of blood flow to the placenta must depend on structural changes and the effect of vasoactive factors. Failure to achieve these adaptations may result in reduced fetoplacental perfusion. The purpose of this study was to determine whether neuronal nitric oxide synthase (nNOS) is expressed in human vascular smooth muscle cells (VSMCs) of the fetoplacental circulation. nNOS has been described as a non-endothelial NOS counterregulating vasoconstriction only in the VSMCs of animal models...