scholarly journals Circulating Heme Oxygenase-1: Not a Predictor of Preeclampsia but Highly Expressed in Pregnant Women Who Subsequently Develop Severe Preeclampsia

2018 ◽  
Vol 2018 ◽  
pp. 1-5 ◽  
Author(s):  
Valéria C. Sandrim ◽  
Mayara Caldeira-Dias ◽  
Heloisa Bettiol ◽  
Marco Antonio Barbieri ◽  
Viviane Cunha Cardoso ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Heme Oxygenase ◽  
Clinical Symptoms ◽  
Severe Preeclampsia ◽  
Urine Samples ◽  
University Hospital ◽  
Enzyme Linked Immunosorbent Assay ◽  
Heme Oxygenase 1 ◽  
Study Cohort ◽  
Potential Biomarker

Preeclampsia is the major cause of maternal and fetal deaths worldwide. Circulating biomarker concentrations to predict preeclampsia must be determined. Therefore, the objective was to evaluate heme oxygenase-1 (HO-1) concentration in both plasma and urine samples from pregnant women before the development of preeclampsia and to identify a potential biomarker for preeclampsia development. We performed a case-control study nested in a prospective study cohort at University Hospital of the Ribeirao Preto Medical School, University of São Paulo (HCFMRP-USP), Ribeirao Preto, Brazil. Of 1400 pregnant women evaluated at 20–25 weeks of gestation, 460 delivered in hospitals outside our institution. Of 940 pregnant women who completed the protocol, 30 developed preeclampsia (cases, 14 cases of severe preeclampsia and 16 cases of mild preeclampsia). Healthy pregnant women (controls, n=90) were randomly selected from the remaining 910 participants. HO-1 concentration was evaluated in plasma/urine samples by using a commercial enzyme-linked immunosorbent assay kit. We found similar HO-1 levels in the plasma and urine for case and control groups. In the subgrouped preeclampsia, lower plasma HO-1 levels were found in mild compared with severe preeclampsia. We conclude that plasma HO-1 levels were not altered at 20–25 weeks of gestation before the manifestation of preeclampsia symptoms. Pregnant women who subsequently develop severe preeclampsia show higher expression of HO-1. This may be indicative of important underlying pathophysiologic mechanisms that differentiate between mild and severe preeclampsia and may possibly be related to a higher prooxidative status even before the development of clinical symptoms.

scholarly journals Upregulation of Heme Oxygenase-1 by Hemin Alleviates Sepsis-Induced Muscle Wasting in Mice

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Xiongwei Yu ◽  
Wenjun Han ◽  
Changli Wang ◽  
Daming Sui ◽  
Jinjun Bian ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Heme Oxygenase ◽  
Muscle Atrophy ◽  
Muscle Wasting ◽  
Cecal Ligation ◽  
Skeletal Muscle Atrophy ◽  
Enzyme Linked Immunosorbent Assay ◽  
Heme Oxygenase 1 ◽  
Protective Effects ◽  
Sod Activity

Hemin, an inducer of heme oxygenase-1 (HO-1), can enhance the activation of HO-1. HO-1 exhibits a variety of activities, such as anti-inflammatory, antioxidative, and antiapoptotic functions. The objective of this study was to investigate the effects of hemin on sepsis-induced skeletal muscle wasting and to explore the mechanisms by which hemin exerts its effects. Cecal ligation and perforation (CLP) was performed to create a sepsis mouse model. Mice were randomly divided into four groups: control, CLP, CLP plus group, and CLP-hemin-ZnPP (a HO-1 inhibitor). The weight of the solei from the mice was measured, and histopathology was examined. Cytokines were measured by enzyme-linked immunosorbent assay (ELISA). Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blotting were used to assess the expression levels of HO-1 and atrogin-1. Furthermore, we investigated the antioxidative effects of HO-1 by detecting malondialdehyde (MDA) levels and superoxide dismutase (SOD) activity. CLP led to dramatic skeletal muscle weakness and atrophy, but pretreatment with hemin protected mice against CLP-mediated muscle atrophy. Hemin also induced high HO-1 expression, which resulted in suppressed proinflammatory cytokine and reactive oxygen species (ROS) production. The expression of MuRF1 and atrogin-1, two ubiquitin ligases of the ubiquitin-proteasome system- (UPS-) mediated proteolysis, was also inhibited by increased HO-1 levels. Hemin-mediated increases in HO-1 expression exert protective effects on sepsis-induced skeletal muscle atrophy at least partly by inhibiting the expression of proinflammatory cytokines, UPS-mediated proteolysis, and ROS activation. Therefore, hemin might be a new treatment target against sepsis-induced skeletal muscle atrophy.

Urinary heme oxygenase-1 as a potential biomarker for early diabetic nephropathy

Nephrology ◽  
2016 ◽  
Vol 22 (1) ◽  
pp. 58-64 ◽  
Author(s):  
Zhenzhen Li ◽  
Yuliang Xu ◽  
Xianghua Liu ◽  
Yali Nie ◽  
Zhanzheng Zhao
Keyword(s):  
Diabetic Nephropathy ◽  
Heme Oxygenase ◽  
Heme Oxygenase 1 ◽  
Potential Biomarker ◽  
Early Diabetic Nephropathy

Heme Oxygenase-1, a Potential Biomarker of Chronic Silicosis, Attenuates Silica-induced Lung Injury

2006 ◽  
Vol 174 (8) ◽  
pp. 906-914 ◽  
Author(s):  
Takashi Sato ◽  
Mitsuhiro Takeno ◽  
Koichi Honma ◽  
Hideyuki Yamauchi ◽  
Yoshiaki Saito ◽  
...  
Keyword(s):  
Lung Injury ◽  
Heme Oxygenase ◽  
Heme Oxygenase 1 ◽  
Potential Biomarker

scholarly journals Heme Oxygenase1 Level in Normotensive Pregnancy and Preeclampsia with Severe Features

2017 ◽  
pp. 128
Author(s):  
Christian Homenta ◽  
John J Wantania ◽  
Juneke J Kaeng
Keyword(s):  
Pregnant Women ◽  
Heme Oxygenase ◽  
P Value ◽  
Heme Oxygenase 1 ◽  
Cross Sectional ◽  
Whitney Test ◽  
Mann Whitney Test ◽  
Significant Difference ◽  
The Relationship ◽  
Normotensive Pregnancy

Objective: To understand the relationship of heme oxygenase-1 (HO-1) level between normotensive pregnancy and preeclampsia with severe features. Method: The cross sectional study was conducted in the Department of Obstetrics and Gynecology, Faculty of Medicine, Universitas Sam Ratulangi/Prof. Dr. R. D. Kandou General Hospital Manado. The subjects consisted of 26 pregnant women with normal blood pressure and 26 women with severe features of preeclampsia. We took the patients’ history, general physical examination, and laboratory assessment. The blood samples were taken from normotensive women more than 20 weeks of pregnancy and preeclamptic women with severe features more than 20 weeks of pregnancy. The data obtained was processed using SPSS 20.0 software. We did the nonparametric Mann-Whitney test to analyze the relationship between heme oxygenase-1 (HO-1) level in normotensive pregnancy and preeclampsia with severe features. Result: The level of heme oxygenase-1 (HO-1) in normotensive pregnant women was at 3.24 (SD 0.58) ng/ml (95% CI 3.00-3.47), and the level of heme oxygenase-1 (HO-1) of preeclamptic women with severe features was 3.92 (SD 0.73) ng/ml (95% CI 3.62-4.21). The result of Mann-Whitney test showed p value of 0.001 which meant that there was significant difference in the level of heme oxygenase- 1 (HO-1) between normotensive women and pre-eclamptic women with severe features. Conclusion: There was the relationship between the level of heme oxygenase-1 (HO-1) and the incidence of preeclampsia with severe features. Keywords: heme oxygenase-1 (HO-1), normotensive pregnancy, preeclampsia with severe features

scholarly journals The Protective Role of Heme Oxygenase-1 (HO-1) in Chronic Subdural Hematoma

Neurosurgery ◽  
2019 ◽  
Vol 66 (Supplement_1) ◽  
Author(s):  
Hui-Tzung Luh
Keyword(s):  
Outer Membrane ◽  
Heme Oxygenase ◽  
Negative Correlation ◽  
Subdural Hematoma ◽  
Chronic Subdural Hematoma ◽  
Significant Negative Correlation ◽  
Enzyme Linked Immunosorbent Assay ◽  
Heme Oxygenase 1 ◽  
Consecutive Series ◽  
Inflammatory Status

Abstract INTRODUCTION Many studies have revealed that angiogenesis and inflammation are closely linked to the pathophysiology of chronic subdural hematoma (CSDH). The development of CSDH is an inflammatory process that begins as a local inflammatory reaction of the dura meter to injury or external stimuli such as blood or CSF. This process causes neovascularization of the outer membrane of CSDH and vascular hyperpermeability. Heme oxygenase-1 (HO-1) is a key enzyme that catalyzes the degradation of heme and produces biliverdin, ferrous iron, and carbon monoxide. HO-1 expression is induced by oxidative stress, and the increasing expression seems to be protective in animal studies. We hypothesized that HO-1 has a protective impact on the severity of CSDH. METHODS This study is designed to correlate the histopathology of the outer membrane of CSDH and HO-1 level in the CSDH hematoma as an indicator of inflammatory status with the clinical presentation of patient and computed tomography (CT) radiological findings of a consecutive series of patients suffered from CSDH. This is a single-center, perspective cohort study. From 2014 to 2017, we enrolled 97 patients with CSDH, who has undergone surgical intervention (burr-hole drainage or craniotomy evacuation). We collect the clinical data, radiological information, and outer membrane and supernatant of the CSDH. We use enzyme-linked immunosorbent assay (ELISA) to measure the concentration of HO-1 in the supernatant of CSDH. RESULTS A significant negative correlation between the HO-1 and the thickness of CSDH is noted (P = .001). On increasing HO-1 by 1 ng/L, the CSDH thickness decreases by 81 mm (P < .005). CONCLUSION Our study demonstrates that HO-1, an important enzyme in angiogenesis and in the inflammation pathway, has a key impact on CSDH severity. A significant negative correlation between the HO-1 and thickness of CSDH has been proved.

Pro- to Anti-angiogenic Ratio in Preeclampsia

2019 ◽  
Vol 15 (2) ◽  
pp. 137-142 ◽  
Author(s):  
Simmi Kharb ◽  
Radha Tiwari ◽  
Smiti Nanda
Keyword(s):  
Growth Factor ◽  
Cord Blood ◽  
Pregnant Women ◽  
Heme Oxygenase ◽  
Venous Blood ◽  
Clinical Manifestations ◽  
Heme Oxygenase 1 ◽  
Soluble Endoglin ◽  
Group 2 ◽  
Endothelial Growth Factor

Background: During fetal development, human placenta undergoes both angiogenesis and vasculogenesis. An imbalance in proangiogenic [placental growth factor (PlGF) and vascular endothelial growth factor] and antiangiogenic factors [soluble fms like tyrosine kinase-1 (sFlt-1), soluble endoglin (sEng)] seems to play an important role in the pathophysiology of preeclampsia. Heme oxygenase-1 HO-1 is induced by ROS (reactive oxygen species) and NO (nitric oxide) and was recently discovered to be involved in angiogenesis. Methods: Hence, the present study was designed to analyze the proangiogenic and antiangiogenic role of heme oxygenase-1 and endoglin in maternal and cord blood of normotensive and preeclamptic women. Fifty pregnant women were selected and grouped as group 1 (control, n=25) comprising of normotensive women immediately after delivery; group 2 (study group) comprising of age -and sex-matched preeclamptic women. Study samples were drawn (maternal venous blood and umbilical cord blood) and heme oxygenase-1 and endoglin levels were analyzed by competitive enzymelinked immunosorbent assay. Results: Maternal and cord blood heme oxygenase-1 levels were significantly elevated in preeclamptic mothers as compared to normotensive pregnant women (p<0.001). Serum and cord blood endoglin levels were significantly lower in preeclamptic women as compared to normotensive pregnant women (p<0.001). HO-1/Eng ratio was drastically doubled in preeclamptics as compared to normotensive pregnant women. In normotensive [HO]/ [Eng+ IGF] were lower in normotensive pregnant and drastically increased in preeclamptics. Conclusion: The findings of a present study indicating a shift towards antiangiogenic profile in women with preeclampsia confirm their possible role to induce characteristic clinical manifestations of preeclampsia such as proteinuria and hypertension.

scholarly journals Interaction Between NOS3 and HMOX1 on Antihypertensive Drug Responsiveness in Preeclampsia

2020 ◽  
Vol 42 (08) ◽  
pp. 460-467
Author(s):  
Valeria Cristina Sandrim ◽  
Marcelo Rizzatti Luizon ◽  
Eliane Pilan ◽  
Mayara Caldeira-Dias ◽  
Fernanda Borchers Coeli-Lacchini ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Antihypertensive Therapy ◽  
Heme Oxygenase ◽  
Antihypertensive Drug ◽  
Enzyme Linked Immunosorbent Assay ◽  
Heme Oxygenase 1 ◽  
Allele Discrimination ◽  
Drug Responsiveness ◽  
Oxide Synthase

Abstract Objective We examined the interaction of polymorphisms in the genes heme oxygenase-1 (HMOX1) and nitric oxide synthase (NOS3) in patients with preeclampsia (PE) as well as the responsiveness to methyldopa and to total antihypertensive therapy. Methods The genes HMOX1 (rs2071746, A/T) and NOS3 (rs1799983, G/T) were genotyped using TaqMan allele discrimination assays (Applied Biosystems, Foster City, CA, USA ), and the levels of enzyme heme oxygenase-1 (HO-1) were measured using enzyme-linked immunosorbent assay (ELISA). Results We found interactions between genotypes of the HMOX-1 and NOS3 genes and responsiveness to methyldopa and that PE genotyped as AT presents lower levels of protein HO-1 compared with AA. Conclusion We found interactions between the HMOX-1 and NOS3 genes and responsiveness to methyldopa and that the HMOX1 polymorphism affects the levels of enzyme HO-1 in responsiveness to methyldopa and to total antihypertensive therapy. These data suggest impact of the combination of these two polymorphisms on antihypertensive responsiveness in PE.

scholarly journals Circulating Tissue Inhibitor of Metalloproteinase-4 levels are not a Predictor of Preeclampsia in the period between 20 and 25 Weeks of Gestation

2018 ◽  
Vol 40 (12) ◽  
pp. 757-762
Author(s):  
Valeria Sandrim ◽  
Jackeline Machado ◽  
Heloisa Bettiol ◽  
Marco Barbieri ◽  
Viviane Cardoso ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Case Control Study ◽  
Clinical Symptoms ◽  
Case Control ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Study Cohort ◽  
Tissue Inhibitor ◽  
A Prospective Study ◽  
Related Proteins ◽  
Control Study

Abstract Objective To evaluate whether the circulating level of tissue inhibitor of metalloproteinase-4 (TIMP-4) in the period between 20 and 25 weeks of gestation is a predictor of preeclampsia. Methods We have performed a case-control study, nested in a prospective study cohort in Ribeirão Preto, in the state of São Paulo, Brazil. Of the 1,400 pregnant women evaluated between 20 and 25 weeks of gestation, 460 delivered in hospitals outside of our institution. Of the 940 pregnant women who completed the protocol, 30 developed preeclampsia. Healthy pregnant women (controls, n = 90) were randomly selected from the remaining 910 participants. From blood samples collected between 20 and 25 weeks of gestation, we performed a screening of 55 angiogenesis-related proteins in 4 cases and 4 controls. The protein TIMP-4 was the most differentially expressed between cases and controls. Therefore, we measured this protein in all cases (n = 30) and controls selected (n = 90). Results There were no differences in the plasma TIMP-4 levels of cases compared with controls (1,144 ± 263 versus 1,160 ± 362 pg/mL, respectively; p > 0.05). Conclusion Plasma TIMP-4 levels were not altered at 20 to 25 weeks of gestation, before the manifestation of clinical symptoms; therefore, they are not good predictors of the development of preeclampsia.

scholarly journals Peptide Charge Derivatization as a Tool for Early Detection of Preeclampsia by Mass Spectrometry—A Comparison with the ELISA Test

Molecules ◽  
2021 ◽  
Vol 26 (23) ◽  
pp. 7102
Author(s):  
Paulina Grocholska ◽  
Andrzej Konieczny ◽  
Zuzanna Kaźmierczak ◽  
Krystyna Dąbrowska ◽  
Karolina Panek-Laszczyńska ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Early Detection ◽  
Pregnant Women ◽  
Early Stage ◽  
Multiple Reaction Monitoring ◽  
Medical Diagnostics ◽  
Elisa Test ◽  
Urine Samples ◽  
Enzyme Linked Immunosorbent Assay ◽  
Peptide Charge

Early detection of any preeclampsia biomarkers may lower the risk of mortality, both for a mother and a child. Our study focuses on techniques for preeclampsia biomarker identification by comparing the results of a method using liquid chromatography mass spectrometry in multiple reaction monitoring mode (LC-MS/MS) with those by the enzyme-linked immunosorbent assay (ELISA) test, as well as by comparing the obtained results with clinical data. In the proposed LC-MS/MS method a tryptic digest peptide charge derivatization strategy was used as a tool for sensitive detection of podocin, i.e., a previously discovered preeclampsia biomarker present in urine samples from pregnant women. Urine samples from pregnant women with diagnosed preeclampsia were collected at different stages of pregnancy and from healthy subjects, and then were analyzed by ELISA test and the proposed method with LC-MS/MS. Charge derivatization of the ε amino group of C-terminal lysine residues in tryptic digests by 2,4,6-triphenylpyrylium salt was performed to increase the ionization efficiency in the LC-MS/MS mode. Podocin was identified at the early stage of pregnancy, while its detection using an ELISA test was not possible. The protocol for urine sample preparation was optimized. Our results show that the proposed method by LC-MS/MS in combination with peptide charge derivatization, provides an ultrasensitive tool for diagnosis of preeclampsia, and provides earlier detection than a clinical diagnosis or ELISA test. The proposed solution may revolutionize medical diagnostics.

Sign in / Sign up

Export Citation Format

Share Document